September 2003
Volume 44, Issue 9
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Eye Movements, Strabismus, Amblyopia and Neuro-ophthalmology  |   September 2003
Comprehensive Evaluation of the Extraocular Muscle Critical Period by Expression Profiling in the Dark-Reared Rat and Monocularly Deprived Monkey
Author Affiliations
  • Georgiana Cheng
    From the Departments of Ophthalmology,
    Visual Sciences Research Center, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio; and
  • Michael J. Mustari
    Yerkes National Primate Research Center and the
    Department of Neurology, Emory University, Atlanta, Georgia.
  • Sangeeta Khanna
    From the Departments of Ophthalmology,
    Visual Sciences Research Center, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio; and
  • John D. Porter
    From the Departments of Ophthalmology,
    Neurology, and
    Neurosciences and the
    Visual Sciences Research Center, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio; and
Investigative Ophthalmology & Visual Science September 2003, Vol.44, 3842-3855. doi:10.1167/iovs.03-0170
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      Georgiana Cheng, Michael J. Mustari, Sangeeta Khanna, John D. Porter; Comprehensive Evaluation of the Extraocular Muscle Critical Period by Expression Profiling in the Dark-Reared Rat and Monocularly Deprived Monkey. Invest. Ophthalmol. Vis. Sci. 2003;44(9):3842-3855. doi: 10.1167/iovs.03-0170.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

purpose. To address the consequences of visual deprivation paradigms in rat (dark rearing) and monkey (monocular deprivation) on extraocular muscle (EOM) development using genome-wide expression profiling.

methods. Serial analysis of gene expression (SAGE) was used to determine alterations in the EOM transcriptome induced by dark rearing of rats from birth to postnatal day 45. Data were compared with previously published normal EOM SAGE library. DNA microarray similarly assessed changes in gene expression patterns of EOMs of monkeys reared from birth to 4 months of age with monocular deprivation.

results. Dark rearing produced changes in expression of 280 transcripts in rat EOM. Of these, 71 were known genes representing functional categories that included energy metabolism/mitochondrial-related (21%), protein synthesis and modification (14%), lipid metabolism (13%), and muscle-related (6%) transcripts. Together, the predominant pattern reflected an energetic shift toward fatty acid β-oxidation and integrated alterations in both myofibers and supportive tissues. The response of monkey rectus muscles to monocular deprivation was considerably less severe.

conclusions. The visual deprivation paradigms used in this study mimic alterations that are associated with the common disorders of strabismus, congenital cataract, and amblyopia. These data show that postnatal EOM maturation is broadly susceptible to changes in activity patterns that are a consequence of visuomotor maldevelopment. The data extend the concept of an EOM-critical period and establish that activity patterns in developing eye movement systems play vital determinant roles in the novel EOM phenotype.

The critical period is a postnatal window during which time patterned retinal activity functions to shape structural and functional properties of the sensory visual system. 1 2 Inappropriate patterns of visual experience during this critical period can perturb the formation and/or pruning of neural connections in visual relay and processing centers and irreversibly alter the ability to produce an accurate representation of the world around us. A key correlate of the critical period is its tight temporal constraints, because identically altered sensory experience later in life does not produce a similar degradation of visual acuity. The critical-period concept has influenced strategies for management of congenital or infantile disorders of vision and eye alignment and is not restricted to the afferent visual system. Visual malexperience also produces less well-understood age-dependent alterations in the oculomotor system. 3 4 5 6 7 8 9 10 Because skeletal muscle is highly responsive to changes in activation patterns, maldevelopment of visuomotor control systems may, in turn, have deleterious consequences for the extraocular muscles (EOMs). 
Evidence for critical periods in any skeletal muscle is limited. Perturbation of postnatal steroid hormone levels or muscle-activation patterns have consequences for maturation of specialized muscle fiber types in laryngeal or jaw musculature. 11 12 13 14 EOM is fundamentally distinct from other skeletal musculature 15 16 17 18 19 and there is evidence that both early and late influences shape EOM myofiber phenotypes. The survival of EOM primordia in an organotypic nerve–muscle coculture system is dependent on trophic support that can be provided by oculomotor, but not spinal, motoneurons. 20 In addition, several EOM traits emerge in parallel with visual and motor system maturation, 21 22 23 24 so that the complex requirements of the five oculomotor control systems (vestibulo-ocular, optokinetic, pursuit, saccadic, and vergence) may shape novel EOM properties by critical period-dependent mechanisms. We previously extended early findings that visual deprivation paradigms alter oculomotor motor unit properties 25 26 27 28 to show that both dark rearing and perinatal compromise of the vestibulo-ocular reflex suppress the postnatal expression of an EOM-specific trait, the EOM myosin heavy chain isoform (Myh13). 29 30  
Here, we used two experimental paradigms to address the EOM critical-period concept: expression profiling with serial analysis of gene expression (SAGE) in dark-reared rats and DNA microarray in monocularly deprived (MD) monkeys. Dark rearing blocks the development of the columnar organization of primary visual cortex. Subsequent analysis of alterations in rat EOMs by SAGE offers the distinct advantage of an unbiased genomic screen, potentially detecting changes in any transcript, that also allows valid comparisons among data sets generated in independent experiments or laboratories. 15 31 MD perturbs ocular dominance column development, putting one eye at a competitive advantage in a way that mimics the visual consequences of human strabismus and amblyopia. Analysis of MD monkey EOMs using DNA microarrays (Affymetrix, Santa Clara, CA) provides a broad-based and unbiased assessment of activity-induced changes. Collectively, data from these approaches identify a broad pattern of EOM phenotype determination by visuomotor activity and lend support to the concept of an EOM critical period. 
Materials and Methods
Animals
Forty-five-day-old male Sprague-Dawley rats (Harlan, Indianapolis, IN) were reared in darkness (DR) from birth. All animal maintenance (cage changing and feeding) was conducted making brief use of a low-intensity lamp with a red filter (1A Safelight Filter; Eastman Kodak, Rochester, NY). Rat rod photoreceptors are barely sensitive to the extreme end of the spectrum, and so a dark-adapted eye may be exposed to fairly high luminance levels of deep red light without loss of adaptation. 32  
Two infant macaque monkeys (Macaca mulatta) were reared from birth to 4 months of age with MD produced by tarsorrhaphy. Two additional normally reared, age-matched monkeys served as the control. The closed eyelids were examined on a daily basis to ensure that opposition remained intact and that no signs of irritation occurred. Monkeys were subjected to visual acuity testing with the forced-choice preferential looking (FPL) method. 33 Assessments of monocular visual acuity were made with Teller acuity cards using prescribed procedures (Vistech Consultants, Inc., Dayton, OH). Each card has black-and-white stripes of a particular width on one side of the card, surrounded by an isoluminant gray background. The monkey was positioned in such a way that its preferential looking toward stripes could be assessed. Infant monkeys naturally look toward stripes at one end of the card rather then the homogenous gray field on the other end. By varying the number of stripes (cycles) per degree of visual angle, acuity can be estimated reliably. In 4-month-old monkeys, we found no measurable acuity in the MD eye, even at the lowest spatial frequency stimulus (0.32 cyc/deg) tested. This finding is consistent with the profound amblyopia associated with MD. In contrast, the visually experienced eye of MD monkeys evinced acuity development similar to that of the age-matched normal control monkeys (i.e., >9.0 cyc/deg). 
All animal procedures were approved by the Institutional Animal Care and Use Committee at Case Western Reserve University (rat and monkey) and Emory University (monkey) and were in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. 
MicroSAGE Protocol and Data Analysis: Rat EOM
At the end of the DR period, all rectus and oblique EOMs were rapidly isolated and removed from both orbits of each of five rats after asphyxiation with carbon dioxide. These are the same muscles that were used in our prior normative study. Tissues were pooled, flash frozen in liquid nitrogen, and stored at −80°C. A SAGE library then was generated using the microSAGE protocol (version 1.0e; http://www.sagenet.org/ provided in the public domain by the Johns Hopkins Oncology Center, Molecular Genetics Laboratory, Baltimore, MD), 34 with modifications as described previously. 15 Briefly, muscle tissue poly (A)+ RNA was reverse transcribed and 14-bp oligonucleotide sequences (tags) were then cut from cDNA with the anchoring enzyme NlaIII (New England Biolabs, Beverly, MA) and released from the 3′ end by using the tagging enzyme BsmFI (New England Biolabs). After SAGE tag isolation and ligation to form ditags, ditags were amplified by PCR, digested by NlaIII, and ligated to form concatemers. Concatenated ditags were purified and cloned into the SphI site of a vector (pZErO-1; Invitrogen, Carlsbad, CA). 
Two thirds of the SAGE tags reported herein were sequenced from plasmids that were randomly selected from bacterial colonies, and one third were from PCR products amplified with M13 forward and reverse primers from colonies that contained inserts more than 616 bp in length. SAGE tag sequencing was performed by Genome Therapeutics Corp. (Waltham, MA; using BigDye terminator chemistry [Applied Biosystems, Inc., Foster City, CA], on a MegaBace automated sequencer [Amersham Biosciences, Piscataway, NJ]). Tag sequences were extracted with eSAGE 1.2a software. 35 SAGE tag sequences containing base calls with Phred (CodonCode Corp, Dedham, MA) quality values less than 20 were not included in the database. 
After sequencing, sequence and location data for each tag were used to identify specific transcripts based on National Center for Biotechnology Information UniGene build number 115 for rat (http://www.ncbi.nlm.nih.gov/UniGene/ provided in the public domain by NCBI). The DR EOM SAGE data then were compared with our existing light-reared (LR; 45-day old rats reared under a normal 12-hour light–dark cycle) EOM SAGE library (available at http://www.ncbi.nlm.nih.gov/geo/ under accession number GSM581; NCBI), 15 after reanalysis of the previous library using eSAGE 1.2a software (http://genome.nhgri.nih.gov/eSAGE/ provided in the public domain by NCBI) and the current UniGene build to ensure equivalent decoding of SAGE tags. eSAGE and the statistical method of Audic and Claverie (http://igs-server.cnrs-mrs.fr/∼audic/significance.html/) 36 were used to identify genes that were differentially expressed in EOMs of the DR versus LR animals. 
DNA Microarray Protocol and Data Analysis: Monkey EOM
Lateral rectus and medial rectus muscles of the MD and control monkeys were independently isolated and compared by using DNA microarray. EOMs from the deprived eye were isolated and processed for DNA microarray, as described previously, 17 37 except that human U133 (A and B) array sets (Affymetrix) were used to evaluate monkey EOMs. These arrays interrogate >33,000 well-documented human transcripts. The probe sets on these human arrays have been shown to have sufficient sequence homology for use in monkeys. 38  
Microarray data were scaled to the same target intensity and analyzed by computer (Microarray Suite; MAS ver. 5.0; Affymetrix). Pair-wise comparisons were made between MD and control monkey EOM samples. Transcripts defined as differentially regulated met the criteria of (1) a consistent increased–decreased call versus control in both replicates, based on Wilcoxon’s signed rank test (the algorithm assesses microarray probe pair saturation, calculates a probability [P] and determines increased, decreased, or no-change calls) and (2) absolute value of the average difference in the multiple of change of 1.8 or more. 
Results
Distribution of DR Rat EOM SAGE Tags
SAGE was used to obtain a quantitative gene expression profile from DR EOM that was then compared with our existing LR EOM SAGE library 15 using eSAGE. Two independent quality-control measurements validate the SAGE library presented herein. First, the average GC content of tags in our DR SAGE library was nearly identical with that of the LR library (DR: 46.4%, LR: 48.0%), indicating the absence of any GC content bias in both (GC bias results from loss of AT-rich regions during tag processing and is defined as GC content ≥55%). Second, linker contamination of our library was very low. The finding of only 0.05% linker sequences was substantially below reports of 0.65% or more in other SAGE libraries. 39  
In SAGE terminology, total SAGE tag number indicates the combined number of copies of all sequenced tags (transcripts). The number of unique tags is equivalent to the total number of distinct transcripts expressed in the library at 1 copy/transcript or more and is the sum of the matched tags (those represented as a known gene or EST in UniGene) and the novel tags (those with identities not recognized by genomics databases). Of the 31,776 total SAGE tags that we accumulated from DR EOM, nearly one-third (10,105) were unique tags and approximately 55% of these were matched tags. Unique tag sequences and counts for the complete DR EOM SAGE library have been deposited to the NCBI Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo/) under accession number GSM3893. Figure 1A summarizes the distribution of matched and novel tags in our DR SAGE library, as a function of copy number. As in most SAGE libraries, the proportion of SAGE tags matching known genes was skewed toward the more abundant tags. Ninety-seven percent of the unique tags in the highest abundance class (≥100 copies/transcript) matched recognized genes or ESTs, whereas only 44.4% of the single-copy tags matched either genes or ESTs in UniGene. Figure 1B shows the percentage of matched genes and ESTs as a function of copy number. 
Comparison of DR and LR Rat EOM SAGE Libraries
The frequency of each tag in our SAGE libraries reflects the relative abundance of the corresponding mRNA in each EOM tissue sample. This feature of SAGE allows digital comparisons between independently generated libraries. The most abundant SAGE tags in DR EOM (detected at a frequency of ≥0.1% of all tags or ≥32 copies/unique tag) also usually were matched tags. Only 5 of the top 96 unique transcripts were novel tags. Similar findings were obtained in the reanalysis of the LR library. Several housekeeping genes (glyceraldehyde-3-phosphate dehydrogenase, β-actin, and lens epithelial protein) were among the most abundant transcripts in both DR and LR libraries, but none was differentially expressed in the two libraries by the conservative criteria used in our study (P ≤ 0.05 and multiple of change ≥3). 
Figure 2 illustrates similarities and differences in unique tag identities detected in the DR and LR EOM SAGE libraries. When single-copy tags were considered, the degree of correspondence in transcripts present in both libraries was low, approximately 20% of unique tags in the combined libraries were shared in DR and LR data. Tags in the intersection of the two libraries were, however, more likely to represent known genes or ESTs (75% matched tags). However, when a threshold of 3 copies per tag or more was applied, 78% of unique tags in the combined data were shared between the two libraries. At this threshold, only 3% (105) of all transcripts represented in both libraries were observed in the DR library only. All 105 of these DR library-specific tags met criteria for significance in comparison with the LR library (P ≤ 0.05). By contrast, 18.6% (564) of unique tags were found only in the larger LR library (only 68 of these differed in expression from the DR library). 
Identity of Differentially Expressed SAGE Tags in DR Versus LR Rat Libraries
Most SAGE tags detected in DR and LR EOMs were represented as single copies; these comprised 71.5% and 72.9% of total tag counts in DR and LR libraries, respectively. Because we used a stringent Phred base-calling threshold, sequencing accuracy was high and most single-copy tags probably represent “real” transcripts. However, at low tag abundance levels there is less confidence in the discrimination capability of the SAGE technique. In identifying differentially regulated transcripts in EOM that result from the dark rearing paradigm, we required a 3-fold change or more and significance level of P ≤ 0.05. By these criteria, 280 unique tags were differentially expressed in DR versus LR EOM, including 172 upregulated and 108 downregulated tags in the DR sample. All 280 unique tags were expressed at three copies or more in at least one of the two libraries. 
Transcripts meeting selection criteria for differential expression in DR EOM were functionally characterized by using gene ontology and other information available from the LocusLink (http://www.ncbi.nlm.nih.gov/LocusLink/ NCBI) and GeneCards (http://bioinfo.weizmann.ac.il/cards/ Weizmann Institute of Science, Rehovot, Israel) databases (Fig. 3 and Table 1 1 1 1 1 1 ). Individual transcripts were assigned to as many as two functional categories. Most of the 280 differentially regulated unique tags represented either ESTs (49%) or uncharacterized novel tags (25%). Of the 71 unique tags representing known genes, the energy metabolism/mitochondrial-related transcript category was the most abundant (21.3% of known genes), followed by the other (15%) protein synthesis/modification (13.8%) and lipid metabolism (12.5%) categories. Muscle-related transcripts constituted only 6.3% of the unique tags representing known genes. Table 1 1 1 1 1 1 lists all unique tags identified as differentially regulated in DR EOM, with corresponding gene identifications and functions. 
Differential Expression in EOMs of MD Monkeys by DNA Microarray
Lateral rectus and medial rectus muscles from control and MD monkeys were independently evaluated (n = 2/experimental group). Because the extent to which MD alters the monocular versus binocular components of conjugate gaze mechanisms is unclear, deprived eye EOMs were compared with those from untreated, age-matched control monkeys. Using DNA microarray, more than 33,000 transcripts were analyzed and data subjected to a strict filter (consistent increase or decrease call across replicates and fold change cutoff of ≥1.8; using Affymetrix MAS 5.0 software). Lateral rectus muscles showed differential regulation of 20 transcripts, with 5 increased and 15 decreased in expression in the muscles of the deprived eye. Twenty transcripts also were differentially regulated in the deprived eye medial rectus, with an equal number up- and downregulated. There was little overlap among the expression patterns in lateral and medial recti, as only glutamine synthase and an uncharacterized mRNA sequence (GenBank BF514079) were differentially regulated in both muscles. Identities and functions of transcripts differentially regulated by MD are shown in Tables 2 and 3
Discussion
Using genome-wide expression profiling with SAGE, we have demonstrated a broad pattern of differential gene expression in rat and monkey EOMs subsequent to experimental perturbations of visual system development. Data show that the altered visuomotor system output associated with dark rearing produced substantial changes in 280 transcripts encompassing a wide range of muscle tissue functions. MD produced alterations in fewer transcripts in monkey EOM. Patterned changes in gene expression in the current study are attributed to the activity dependence of maturing EOM and its associated tissues. These data provide support for the EOM critical-period concept, suggesting that EOM maturation is regulated, at least in part, by the activity patterns of developing visuomotor systems. 
The visual deprivation models and gene profiling techniques used were selected to take full advantage of the strengths of each model. Because the rat has a limited binocular field, we chose dark rearing to globally suppress the development of primary visual cortex. SAGE provides excellent in-depth expression analysis and our previously published, normative rat EOM SAGE library served as a control in our study. By contrast, the substantial binocular field of the macaque monkey allowed us to use the more specific, clinically relevant strategy of MD. A SAGE database is not available for the monkey, and the human database could not be used, because species sequence differences become problematic when gene identity is based on a very short SAGE tag sequence. Thus, human microarrays (Affymetrix), which survey approximately 33,000 genes and ESTs and have been demonstrated to have sufficient sequence homology for use in monkey, 38 were used. Collectively, the visual deprivation paradigms and expression profiling tools used in the study are well accepted and provide considerable insight into transcriptional changes in EOM that result from visual system maldevelopment. 
SAGE and DNA microarray are formidable tools for assessing the entire transcriptome of cell or tissue types. In an in vivo assessment of the EOM expression profile, we acknowledge that multiple cell types (e.g., muscle, neural, vascular, connective tissue, resident inflammatory cells) contributed to the SAGE and microarray data generated herein, and it is likely that visual deprivation has produced transcriptional changes in supportive tissues as well as myofibers. However, muscle is an integration of a wide array of tissue types and the complex systems biology question of how activity-dependent regulation of the novel EOM phenotype is achieved cannot be addressed only through study of isolated myofibers. In our study, we used stringent controls and data acceptance criteria to provide a conservative estimate of genes that may participate in an EOM critical period. 
In serving as the effector organ for the wide dynamic range of eye movement control systems ranging from pursuit and vergence movements of less than 1 deg/sec to saccades that can exceed 800 deg/sec, while maintaining precise interocular alignment and foveation of visual targets, the EOMs arguably face the most extreme demands of any skeletal muscle. Thus, the baseline morphology and gene expression profile of EOM is fundamentally different from that of other striated muscles, with this muscle group encompassing traits from both cardiac and skeletal musculature in adapting to the eye movement role. 15 16 17 18 19 A key gap in EOM biology is the lack of understanding of developmental mechanisms that modulate assembly of the atypical EOM fiber types and their associated supporting tissues. The correlation between the complexity and diversity of eye movement control systems and the novel properties of the EOMs suggested to us that the two were mechanistically linked, with the functional demands placed on EOM acting as direct determinants of the muscle phenotype. 
In prior studies, we demonstrated activity dependence in the postnatal appearance of a key EOM trait, the EOM-specific myosin (Myh13). 29 30 That Myh13 is tightly regulated is seen in both its late expression 24 and spatial restriction to only the perijunctional regions of specific EOM fiber types. 24 40 41 Interference in maturation of either the visual afferent system 29 or the vestibulo-ocular reflex 30 led to suppression of Myh13 mRNA, presumably as a result of decreased oculomotor motoneuron activity in both paradigms. Neither manipulation was effective in downregulation of Myh13 when applied in adult rats. Collectively, these data established that Myh13 expression by EOM myofibers requires specific signaling, most likely neural activity patterns, during a postnatal temporal window and thereby suggests the existence of an EOM critical period. We did not, however, detect changes in Myh13 here. This may be the result of the very restricted distribution of Myh13, the relatively low level of Myh13 suppression, and/or differences in the sensitivity of the techniques used. In particular, we have taken a very stringent approach toward analysis of the expression profiling data presented herein that may lead to false negatives. 
In this study, we extended the breadth of EOM transcripts that are influenced by the alterations in visuomotor activity that accompany dark rearing. Each differentially regulated transcript is a candidate for the EOM critical period. The 280 distinct transcripts that met selection criteria for differential regulation in DR rat EOM were not restricted to myofiber-specific genes, but included genes shared by myofibers and other cell types and genes usually associated with other tissue types. Several muscle-specific genes (upregulated: sarcosin, triadin 1, calpain 3, and cardiac calsequestrin; downregulated calponin 3) were differentially regulated in DR EOM. EOM is known to express cardiac muscle transcript isoforms, 17 19 42 and dark rearing increased the expression of two of these, triadin 1 and cardiac calsequestrin. Several transcripts that function as cytoskeletal elements also were differentially expressed (e.g., upregulated: dynein-associated protein RKM23 and afadin; downregulated: calponin 3). Changes in Myh13 did not reach significance. 
The most substantial change in DR EOM involved transcripts related to intermediary and energy metabolism (>21% of the known genes differentially expressed in DR). A key rate-limiting enzyme of glycolysis (phosphofructokinase-muscle isoform) was downregulated, whereas several transcripts related to lipid metabolism were upregulated (dodecenoyl-CoA delta isomerase, transaldolase 1, malic enzyme 1, enoyl-CoA hydratase short chain 1, and acyl-CoA oxidase) or downregulated (acetoacetyl-CoA synthetase, thyroid hormone responsive protein, and fatty acid-CoA ligase long chain 5). Upregulation of acyl-CoA oxidase and enoyl-CoA hydratase short chain 1 is particularly compelling, because these represent the first two steps of the pathway for β-oxidation of fatty acids. Three ESTs with homology to β-oxidation pathway transcripts (acyl-CoA dehydrogenase, acyl-CoA thioester hydrolase, and carnitine/acylcarnitine translocase) also were upregulated in DR EOM. These data suggest a shift in DR EOM toward an energy mode that is normally predominant in cardiac, but not skeletal, muscle. Consistent with the energetics theme, a total of seven mitochondria-related transcripts with a broad range of functions were induced in DR EOM. Taken together, the shifts in several muscle-specific and energy metabolism protein transcripts are consistent with the alteration of usage patterns of the EOMs. 
DR-induced changes in transcripts that function in protein translation and posttranslational modification were prominent (13.8% of known genes identified in DR EOM), but due to the broad expression of these genes the involved cell types cannot yet be established. Among nonmuscle transcripts differentially expressed in DR EOM were two downregulated collagen genes (collagen type 1 alpha 1 and procollagen C-proteinase enhancer protein). The high percentage of ESTs and novel tags in our library (collectively 74% of all detected transcripts) makes it difficult to assess the full scope of the EOM critical period at this time. Several of the ESTs have sequence homology to genes that fit the altered cytoskeletal and mitochondrial transcript themes. As genomic databases are completed, the EST and novel tag data presented in this report can be reassessed from a broader knowledge of the identities of differentially regulated transcripts. 
The patterned changes in gene expression of MD monkey EOMs were considerably less severe than in DR rats. Although control monkey lateral and medial rectus muscles do not differ in baseline gene expression patterns (unpublished data), they exhibited differential expression responses to MD. Differences in the lateral and medial rectus response are not unexpected, because the loss of binocular vision in MD disrupts disjunctive fusional vergence movements, whereas conjugate eye movements driven by the nondeprived eye appear to be normal. 7 Moreover, both visual pursuit and optokinetic eye movements exhibit a temporal–nasal asymmetry that is accentuated in visual maldevelopment. The different affect on horizontal rectus muscles may be a consequence of such differences in conjugate or disjunctive eye movements. As in DR rats, few muscle-specific transcripts were altered in monkey EOMs; increased expression of MEF2C in the MD medial rectus is consistent with myogenesis. Extracellular matrix components were downregulated in both medial and lateral recti, as they were in DR rat EOMs. Two transcripts related to posttranslational protein modification (HSPB1 and PPIF) were upregulated in MD medial rectus, consistent with differential regulation of multiple genes in this class in DR rat EOM. Few transcripts linked to mitochondrial function or energy metabolism were differentially regulated in MD EOMs (PDK4, a glycolysis regulator, was repressed in lateral rectus; TKT, a pentose phosphate pathway enzyme, and OGDH, a tricarboxylic acid cycle enzyme, were induced in medial rectus). Thus, the shift in energy metabolism that was seen in DR rats was not observed in the MD monkey. Genes shared between the medial and lateral recti of MD monkeys and between the rat DR and monkey MD models are indicated in Tables 2 and 3 . Although only two transcripts were shared between MD lateral and medial recti and only one was shared between MD monkey and DR rat, there was sharing of functional categories of differentially regulated transcripts. 
We suggest that the nature and severity of the gene expression changes in the MD monkey versus the DR rat are consequences of inherent differences in the visual deprivation paradigms. Rather than the prevention of primary visual cortex (V1) maturation that occurs in DR, MD alters ocular dominance column maturation in V1, while preserving at least a monocular drive to eye movement control systems from the non-deprived eye. Lennerstrand and Hansen 26 and Lennerstrand 27 28 observed decreases in the contraction speed and fatigue resistance in EOMs of MD cats, but saw no accompanying shift in muscle fiber type composition. Similarly, DR rat EOMs show a slowing of contraction speed, 43 but neither DR nor MD altered the expression of many muscle fiber–specific transcripts. Moreover, congenitally strabismic monkeys, which share visual deficits with MD, exhibit modest morphologic changes in specific EOM fiber types. 44 Taken together, the differences in expression signatures obtained from DR and MD paradigms then suggest that EOM requires visuomotor-driven activity for proper development, but that any MD-induced functional adaptations in EOM are associated with transcriptional changes that are either modest or largely below the threshold of DNA microarray. 
Conclusions
The DR and MD paradigms used in the current study mimic alterations that are associated with the common disorders of strabismus, congenital cataract, and amblyopia. Our data show that postnatal EOM maturation is broadly susceptible to visuomotor maldevelopment, suggesting that postnatal eye movement system activity plays a vital determinant role in the maturation of the novel EOM phenotype. Differentially regulated transcripts identified herein represent new gene candidates for an EOM critical period. Yet, the full nature of this critical period is only partially understood, because many of the transcripts detected in DR rat EOM represent ESTs or novel SAGE tags. Collectively, our findings then extend the concept of an EOM critical period and suggest that the nature of visual deprivation is an important factor in this critical period. 
 
Figure 1.
 
Frequency distribution histograms of SAGE tags derived from DR rat EOM. (A) Semilog plot of the frequency of SAGE tags detected at specific abundance levels. Matched tags are those that are represented in genomics databases as known genes or ESTs. Novel tags represent mRNA sequences not found in these databases. Novel tags were most abundant among the single-copy group and declined as a percentage of all tags with increasing copy number. (B) Plot showing the frequency of matched tags among tag abundance groups.
Figure 1.
 
Frequency distribution histograms of SAGE tags derived from DR rat EOM. (A) Semilog plot of the frequency of SAGE tags detected at specific abundance levels. Matched tags are those that are represented in genomics databases as known genes or ESTs. Novel tags represent mRNA sequences not found in these databases. Novel tags were most abundant among the single-copy group and declined as a percentage of all tags with increasing copy number. (B) Plot showing the frequency of matched tags among tag abundance groups.
Figure 2.
 
Venn diagrams representing SAGE tag distribution patterns in the dark-reared (DR) and light-reared (LR) rat EOM libraries. (A) Distribution between the two libraries when all SAGE tag copy number categories were considered. Note overlap represents only 19.7% of the total number of unique tags. (B) Distribution between the two libraries when SAGE tag copy number was restricted to three copies per tag or more. Overlap between the two libraries was 78%.
Figure 2.
 
Venn diagrams representing SAGE tag distribution patterns in the dark-reared (DR) and light-reared (LR) rat EOM libraries. (A) Distribution between the two libraries when all SAGE tag copy number categories were considered. Note overlap represents only 19.7% of the total number of unique tags. (B) Distribution between the two libraries when SAGE tag copy number was restricted to three copies per tag or more. Overlap between the two libraries was 78%.
Figure 3.
 
Functional category distribution of SAGE tags detected as differentially regulated in DR rat EOM. Top: Functional distribution of all 280 unique tags. Bottom: Functional distribution of the 71 matched tags that have been linked to known genes. Mus, muscle-related; Cyto, cytoskeletal; Met, metabolism/mitochondrial related; Lip, lipid metabolism; CS/ECM, cell surface/extracellular matrix; Sig, signaling/cell–cell communication; C/D, cell proliferation/death; Trans, transcription; Pro, protein synthesis/modification; Rec, receptor/transporter/ion channel; Imm, immune response; Oth, other/unknown.
Figure 3.
 
Functional category distribution of SAGE tags detected as differentially regulated in DR rat EOM. Top: Functional distribution of all 280 unique tags. Bottom: Functional distribution of the 71 matched tags that have been linked to known genes. Mus, muscle-related; Cyto, cytoskeletal; Met, metabolism/mitochondrial related; Lip, lipid metabolism; CS/ECM, cell surface/extracellular matrix; Sig, signaling/cell–cell communication; C/D, cell proliferation/death; Trans, transcription; Pro, protein synthesis/modification; Rec, receptor/transporter/ion channel; Imm, immune response; Oth, other/unknown.
Table 1.
 
Differentially Regulated Transcripts in Dark-Reared Rat EOM
Table 1.
 
Differentially Regulated Transcripts in Dark-Reared Rat EOM
Tag LR DR DR/LR P Unigene (RS) Gene Name Function
TCACTTTCTA 1 11 18.6 1.2E-04 None Novel tag Nov
GCAGTGCAAA 1 9 15.2 0.001 12436 ESTs, highly similar to hypothetical protein; FLJ10055[Homo sapiens] EST
GTGATAGACA 1 9 15.2 0.001 2944 Peroxiredoxin 6 (Prdx6) Oth
TGGGAACTGT 1 9 15.2 0.001 17567 ESTs, weakly similar to FZD2_RAT; Frizzled 2 precursor (Frizzled-2) (Fz-2); (rFz2) [Rattus norvegicus] EST
ACTGACAAAA 0 8 13.5 2.7E-04 12038 ESTs EST
TACATAGCCA 1 8 13.5 0.002 11363 Pyruvate dehydrogenase kinase 2 (Pdk2) Met
CTCCTGCAGT 1 7 11.8 0.004 3682 ESTs, moderately similar to ESTD_HUMAN esterase D[H. sapiens] EST
TGAGCTCTGA 1 7 11.8 0.004 None Novel tag Nov
CAACCCCAAA 1 6 10.1 0.011 6541 ESTs, weakly similar to RP3A_RAT Rabphilin-3A[R. norvegicus] EST
CAGCTATTGT 0 6 10.1 0.002 36855 ESTs, highly similar to JC6161 kinesin-associated protein KAP3 splice form A EST
CATACGCTCA 1 6 10.1 0.011 None Novel tag Nov
CTCGAGCGGC 0 6 10.1 0.002 55376 EST EST
GCACTTGCTG 1 6 10.1 0.011 3996 ESTs, highly similar to OBRG_RAT; leptin receptor gene-related protein (OB-R gene related protein) (OB-RGRP)[R. norvegicus] EST
GCATCAGTAC 0 6 10.1 0.002 16830 ESTs EST
GTGTGGAATC 1 6 10.1 0.011 839 FXYD domain-containing ion transport regulator (Fxyd6) Rec
AAATAAATGT 0 5 8.4 0.005 9668 Myelin-associated glycoprotein (Mag) Oth
8978 ESTs, weakly similar to B34252 acyl-CoA dehydrogenase(EC 1.3.99.3) short-chain-specific precursor, hepatic
CAAAATAGTT 1 5 8.4 0.025 None Novel tag Nov
CAGCAATAAA 3 15 8.4 7.2E-05 15530 ESTs EST
CAGCTATGCA 1 5 8.4 0.025 7258 ESTs, highly similar to male-specific lethal-3 H.log 1 (Drosophila) [Mus musculus] EST
CCCATAATCC 2 10 8.4 0.001 3380 Synaptic glycoprotein SC2 (SC2) Oth
CTATTTAATT 1 5 8.4 0.025 8763 ESTs, weakly similar to TXTP_RAT tricarboxylate transport protein, mitochondrial precursor (Citrate transport protein) (CTP) (Tricarboxylate carrier protein) [R. norvegicus] EST
CTCCTGAAGG 1 5 8.4 0.025 2784 ESTs, highly similar to UB6B_MOUSE; ubiquitin-conjugating enzyme E2-23 kDa; (ubiquitin-protein ligase; ubiquitin carrier protein) [M. musculus] EST
CTTTTTATAC 0 5 8.4 0.005 13643 ESTs, highly similar to calcium binding atopy-related autoantigen 1; atopy-related autoantigen [H. sapiens] EST
1040 ESTs, highly similar to G0S2_MOUSE; putative lymphocyte G0/G1 switch protein 2 (G0S2-like protein) [M. musculus]
GATGCCTCCC 0 5 8.4 0.005 None Novel tag Nov
GCAGAGAATG 1 5 8.4 0.025 4077 ESTs, weakly similar to A34866 T-cell surface protein RT6.2 precursor EST
GCTGGTTCCA 0 5 8.4 0.005 9726 Calpain 3 (Capn3) Mus
GGCTACGGTT 1 5 8.4 0.025 None Novel tag Nov
GGGCTGCCCA 1 5 8.4 0.025 3053 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member2 Oth
38063 ESTs, weakly similar to sugar transporter[Caenorhabditis elegans] EST
GTAGGAAGAT 0 5 8.4 0.005 33378 ESTs, highly similar to feminization 1 H.log a (C. elegans); feminization 1 a H.log [C. elegans; M. musculus] EST
GTTTCGTGGT 1 5 8.4 0.025 17086 ESTs EST
TACCCCTTTA 1 5 8.4 0.025 None Novel tag Nov
TCACCTTGTT 1 5 8.4 0.025 31796 Acyl-coA oxidase (Acoal) Met, Lip
TCCTGGCAGT 1 5 8.4 0.025 None Novel tag Nov
TGAGCAGACG 1 5 8.4 0.025 35504 ESTs EST
TGCCATTGCA 0 5 8.4 0.005 32316 ESTs, weakly similar to sialyltransferase 3; sialyltransferase)[R. norvegicus] EST
TGTTTGCAGA 0 5 8.4 0.005 22183 ESTs, moderately similar to hypothetical protein dJ12208.2[H. sapiens] EST
TTCACAAAGG 0 5 8.4 0.005 1276 Proteasome (prosome, macropain) subunit, alpha type 5 (Psma5) Pro
85470 ESTs, weakly similar to JX0229 multicatalytic endopeptidase complex (EC 3.4.99.46) zeta chain
TTGGAATCCA 0 5 8.4 0.005 20119 ESTs EST
TTTTGAGGAC 0 5 8.4 0.005 3496 ESTs EST
ATACTGACAT 2 9 7.6 0.003 None Novel tag Nov
(continues)
Table 1A.
 
(continued). Differentially Regulated Transcripts in Dark-Reared Rat EOM
Table 1A.
 
(continued). Differentially Regulated Transcripts in Dark-Reared Rat EOM
Tag LR DR DR/LR P Unigene (RS) Gene Name Function
AAAAAAGAAA 0 4 6.8 0.014 19930 ESTs, moderately similar to RIKEN cDNA 2310079N02[M. musculus] EST
AAGGTCTTTA 0 4 6.8 0.014 13244 ESTs EST
ACCATCCCTT 0 4 6.8 0.014 None Novel tag Nov
ATAAAACCAG 0 4 6.8 0.014 None Novel tag Nov
CACAAGCGGT 0 4 6.8 0.014 None Novel tag Nov
CCCCCAATTC 0 4 6.8 0.014 31977 Vesicle-associated membrane protein 2 (Vamp2) Oth
6430 ESTs
3748 ESTs, highly similar to gamma tubulin complex component; KIAA1669 protein; similar to Xenopus gamma tubulin interacting protein (yeast SPC98 H.log) [H. sapiens]
CTGAGGGAGG 0 4 6.8 0.014 24472 ESTs, weakly similar to hypothetical protein MGC13119[H. sapiens] EST
CTGATCCAGT 0 4 6.8 0.014 11946 Ubiquitin fusion degradation I-like Pro
GAAGTTGTGC 0 4 6.8 0.014 12833 ESTs, highly similar to T43442 hypothetical protein DKFZp43p1514 EST
GCAACCAAAA 0 4 6.8 0.014 37542 Suppressor of K+ transport defect 3 Oth
GCTGTTCTGT 0 4 6.8 0.014 3628 Glutamate oxaloacetate transaminase 2; mitochondrial (aspartate aminotransferase 2) (Got2) Met
GGCGGGTGGA 0 4 6.8 0.014 20220 ESTs EST
GTATGCCCCC 0 4 6.8 0.014 None Novel tag Nov
GTCCAAGATT 0 4 6.8 0.014 72495 ESTs EST
GTGATGCCAC 0 4 6.8 0.014 22278 ESTs, highly similar to CGE0_HUMAN; protein CGI-140 (protein PTD008) [H. sapiens] EST
GTGCTAACAA 0 4 6.8 0.014 44114 ESTs, highly similar to AT10_MOUSE ADAMTS-10(a disintegrin and metalloproteinase with thrombospondin motifs 10; ADAM-TS 10, ADAM-TS10) [M. musculus] EST
GTTAGGTAGG 0 4 6.8 0.014 3421 Adenylate kinase 2 (Ak2) Met
TAACCAATCA 0 4 6.8 0.014 3548 ESTs, highly similar to small GTP-binding protein rab5[R. norvegicus] EST
TAGGCCACCA 0 4 6.8 0.014 None Novel tag Nov
TATGTGGAAT 0 4 6.8 0.014 7983 ESTs, highly similar to catenin alpha-like 1; alpha-catenin related protein [M. musculus] EST
TGCCAAGCCC 0 4 6.8 0.014 19513 ESTs EST
TGGATCTGAG 0 4 6.8 0.014 72471 ESTs EST
TGTGACAGTG 0 4 6.8 0.014 13976 ESTs EST
TTAATTCATT 2 8 6.8 0.007 2230 Translocase of inner mitochondrial membrane 23 H.log(yeast; Timm23) Met
GACGCCCCCC 3 11 6.2 0.002 None Novel tag Nov
CTGTGCTCGA 2 7 5.9 0.015 26731 ESTs EST
GGAAGTCAGG 2 7 5.9 0.015 None Novel tag Nov
GCGAAAGAAT 3 10 5.6 0.004 6847 Enoyl Coenzyme A hydratase, short chain 1 (Echs1) Met, Lip
GCCCCGGTGC 4 13 5.5 0.001 38221 ESTs, highly similar to cardiac abnormality/abnormal facies (CATCH22); microdeletion syndrome [M. musculus] EST
AAAATCAAGT 0 3 5.1 0.038 19102 ESTs, weakly similar to S21976; probable RNA-directed DNA polymerase (EC 2.7.7.49; clone MH2C) EST
AAGGAAATAA 2 6 5.1 0.032 29754 Prohibitin C/D
ACAGACACTT 0 3 5.1 0.038 8129 ESTs EST
ACATCGTGCG 0 3 5.1 0.038 53919 ESTs, highly similar to human SLC21A6 EST
ACCGTTATAA 0 3 5.1 0.038 1722 Lysosomal-associated membrane protein 2 (Lamp2) Oth
AGAGAAGGGT 0 3 5.1 0.038 44362 Inositol 1,4,5-trisphosphate 3-kinase B (ltpkb) Sig
AGGGAGCCGC 0 3 5.1 0.038 None Novel tag Nov
ATAAGCACAT 0 3 5.1 0.038 None Novel tag Nov
ATAAGTCATA 0 3 5.1 0.038 None Novel tag Nov
ATGATTTAAC 0 3 5.1 0.038 41151 ESTs EST
ATGGGTGGAA 0 3 5.1 0.038 36164 ESTs, highly similar to hypothetical protein FLJ20211[H. sapiens] EST
ATGTGTATGT 0 3 5.1 0.038 2560 ESTs EST
CAAAGACAAT 0 3 5.1 0.038 40403 ESTs, highly similar to HSPC038 protein [H. sapiens] EST
CATAACACAT 0 3 5.1 0.038 None Novel tag Nov
CCGGGGTGAT 0 3 5.1 0.038 None Novel tag Nov
CTATGTAGAC 0 3 5.1 0.038 23858 ESTs, moderately similar to HCDI protein [H. sapiens] EST
CTGCTGTAAT 0 3 5.1 0.038 55106 Glutamate dehydrogenase (Glud1) Oth
CTGTGTGATC 2 6 5.1 0.032 22047 ESTs, moderately similar to T46271 hypothetical protein DKFZp564P2163.1 EST
CTTCCCACTG 0 3 5.1 0.038 2274 Ubiquitin conjugating enzyme E2I (Ube2i) Pro
CTTGCTTTTT 0 3 5.1 0.038 44161 Lamin A (Lmna) Oth
CTTTGAAAGG 0 3 5.1 0.038 None Novel tag Nov
(continues)
Table 1B.
 
(continued). Differentially Regulated Transcripts in Dark-Reared Rat EOM
Table 1B.
 
(continued). Differentially Regulated Transcripts in Dark-Reared Rat EOM
Tag LR DR DR/LR P Unigene (RS) Gene Name Function
GAAAAGTCGA 0 3 5.1 0.038 20571 ESTs EST
GACACAGAAA 0 3 5.1 0.038 41880 ESTs EST
GAGACTCTAC 0 3 5.1 0.038 9091 ESTs, highly similar to KIAA0710 gene product [H. sapiens] EST
GAGGATGCTG 0 3 5.1 0.038 71588 EST EST
GATAAACACA 0 3 5.1 0.038 43517 ESTs EST
GATCACCTGT 2 6 5.1 0.032 17012 ESTs, highly similar to MGPI_MOUSE Microfibril-associated glycoprotein precursor (MAGP) (MAGP-1) [M. musculus] EST
GATGAGGGTC 0 3 5.1 0.038 18199 ESTs, highly similar to A41784 tumor necrosis factor-alpha-induced protein B12 EST
GATTCTGCCC 0 3 5.1 0.038 41894 ESTs EST
GCACACACAT 0 3 5.1 0.038 None Novel tag Nov
GCACGAACAT 0 3 5.1 0.038 7295 EST EST
GCTGAGACTG 0 3 5.1 0.038 11534 ESTs, highly similar to TYRO protein tyrosine kinase binding protein; killer cell activating receptor associated protein[M. musculus] EST
GGACACCAAA 3 9 5.1 0.008 2938 Mitochondrial ribosomal protein L 17 Pro
GGAGTAGATT 0 3 5.1 0.038 3519 Malic enzyme 1, soluble (Mel) Met, Lip
GGCTATTTTA 0 3 5.1 0.038 3988 EST EST
GGCTCAGCTC 0 3 5.1 0.038 None Novel tag Nov
GGGCCATTAG 3 9 5.1 0.008 58 Afadin (AF-6) Sig, Cyto
GGTCCTACCC 0 3 5.1 0.038 33467 ESTs EST
GTCGCTTCTG 0 3 5.1 0.038 6199 ESTs, moderately similar to U2AG_MOUSE Splicing factor U2AF 35 kDa subunit (U2 auxiliary factor 35 kDa subunit) (U2 snRNP auxiliary factor small subunit) [M. musculus] EST
GTGACGGCCT 0 3 5.1 0.038 None Novel tag Nov
GTGCGGGCTC 0 3 5.1 0.038 39333 Endosulfine alpha (Ensa) Rec
GTTTGAGCAT 0 3 5.1 0.038 17490 ESTs EST
TAAAATGTAG 0 3 5.1 0.038 None Novel tag Nov
TAACGTCTAG 0 3 5.1 0.038 59806 EST EST
TAGGTCACAG 0 3 5.1 0.038 None Novel tag Nov
TATTAGTTAT 0 3 5.1 0.038 26749 ESTs EST
TCCAACTTCT 0 3 5.1 0.038 None Novel tag Nov
TCTCTGCCTG 0 3 5.1 0.038 11272 SH3 domain binding protein CR16 Sig
TCTGCCCTCC 0 3 5.1 0.038 25440 ESTs EST
TCTTCTGTGG 0 3 5.1 0.038 3616 ESTs EST
TGAACAAAAA 0 3 5.1 0.038 8839 EST EST
TGACATACGT 0 3 5.1 0.038 7910 ESTs EST
TGATACGATT 0 3 5.1 0.038 3694 ESTs, highly similar to TRAP/Mediator complex component TRAP25 [H. sapiens] EST
TGCACGCGTC 0 3 5.1 0.038 2315 Translin-associated factor X Oth
TGCTGAATCA 0 3 5.1 0.038 25036 ESTs EST
TGGAAAAAAA 0 3 5.1 0.038 35208 ESTs, moderately similar to UCRX_HUMAN ubiquinol-cytochrome C reductase complex 7.2 kDa protein (cytochrome C1, nonheme 7 kDa protein; complex III subunit X; 7.2 kDa cytochrome c1-associated protein subunit; HSPC119) [H. sapiens] EST
TGGGGTCTCA 0 3 5.1 0.038 35476 ESTs EST
TGGGGTTTAT 0 3 5.1 0.038 4107 ESTs EST
TGTGCACCAG 0 3 5.1 0.038 12034 ESTs EST
TGTGTAATGT 0 3 5.1 0.038 758 ESTs, moderately similar to RIKEN cDNA 4833415N24[M. musculus] EST
TGTTTTGGAA 0 3 5.1 0.038 8157 ESTs, highly similar to T08778 hypothetical protein DKFZp58611520.1 EST
TTAAGTGTTG 0 3 5.1 0.038 37781 ESTs, moderately similar to G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein (GIT1) [R. norvegicus] EST
TTCTGCTCCT 0 3 5.1 0.038 21976 ESTs EST
TTGAAGTGGT 0 3 5.1 0.038 73073 ESTs, weakly similar to intersectin (SH3 domain protein 1A) [R. norvegicus] EST
TTGACGGTGG 0 3 5.1 0.038 6834 ESTs EST
TTGATGTTGA 0 3 5.1 0.038 2197 ESTs, moderately similar to erythroblast macrophage protein [M. musculus] EST
TTGTCTGTAA 0 3 5.1 0.038 28239 ESTs EST
TTTAAAGGAA 0 3 5.1 0.038 None Novel tag Nov
TTTACTGGGT 0 3 5.1 0.038 2469 ESTs, highly similar to ZK652.3.p [C. elegans] EST
TTTATAAGTT 0 3 5.1 0.038 17999 ESTs, highly similar to OM40_MOUSE; Probable mitochondrial import receptor subunit TOM40 H.log (translocase of outer membrane 40 kDa subunit H.log) [M. musculus] EST
(continues)
Table 1C.
 
(continued). Differentially Regulated Transcripts in Dark-Reared Rat EOM
Table 1C.
 
(continued). Differentially Regulated Transcripts in Dark-Reared Rat EOM
Tag LR DR DR/LR P Unigene (RS) Gene Name Function
TTTGCATATT 0 3 5.1 0.038 19104 ESTs, weakly similar to ACTB_HUMAN; actin, cytoplasmic 1 (beta-actin) [R. norvegicus] EST
TTTTGAATGC 0 3 5.1 0.038 15531 ESTs EST
CTGAGTGTGG 7 19 4.6 2.2E-04 3902 ESTs, highly similar to B32394 succinate dehydrogenase (ubiquinone) (EC 1.3.5.1) 27K iron-sulfur protein EST
TTAATAAAAG 4 11 4.6 0.005 3393 T-cell activation protein-related (PGR1) Imm
39 ESTs, highly similar to Y184_HUMAN HYPOTHETICAL PROTEIN KIAA0184 [H. sapiens]
CTACACTGGC 3 8 4.5 0.018 41863 Triadin 1 Mus
GGGCACAGGA 3 8 4.5 0.018 7680 ESTs, highly similar to Fas-activated serine/threonine kinase [M. musculus] EST
GTCCCAAGGA 3 8 4.5 0.018 4005 Dodecenoyl-coenzyme A delta isomerase (Dci) Met, Lip
80835 Rat mRNA for delta3, delta2-enoyl-CoA isomerase
GTTCCGACAG 3 8 4.5 0.018 8104 ESTs EST
TGTGGTGGAG 3 8 4.5 0.018 24190 ESTs EST
CAGATCAGAA 5 13 4.4 0.003 14050 ESTs EST
CAGATCTTTG 4 10 4.2 0.010 3761 Ubiquitin C (UBA52) Pro
4300 Ubiquitin A-52 residue ribosomal protein fusion product 1
GACTTGGTCA 4 10 4.2 0.010 None Novel tag Nov
TGGGTTAGAC 5 12 4.1 0.005 919 ESTs, highly similar to prefoldin 1; prefoldin subunit 1[H. sapiens] EST
CTGAGAAATA 3 7 3.9 0.037 8792 ESTs, highly similar to AC48_MOUSE 48; kDa acyl-CoA thioester hydrolase, mitochondrial precursor(p48; Mt-ACT48; protein U8) [M. musculus] EST
GTGAAGAGTT 3 7 3.9 0.037 18515 ESTs, weakly similar to ubiquitin specific protease 2[R. norvegicus] EST
TAAACCAGGT 3 7 3.9 0.037 7349 ESTs EST
TGAAATTTTG 3 7 3.9 0.037 3136 Transaldolase 1 Met, Lip
TAGGGTTACA 4 9 3.8 0.020 28875 Sarcomeric muscle protein (sarcosin) Mus
TTGTGATTAC 4 9 3.8 0.020 21198 MSI Mus
AGCAGAGAAT 5 11 3.7 0.011 4180 ESTs EST
ATACTGACCT 13 27 3.5 1.1E-04 None Novel tag Nov
GTAACACATA 10 21 3.5 0.001 61080 ESTs, weakly similar to JC6197 stromelysin 3 (EC 3.4.24) EST
CAGACCTTGG 5 10 3.4 0.021 3560 Dynein-associated protein RKM23 (Km23) Cyto
CGCTGGGATG 5 10 3.4 0.021 8526 ESTs, weakly similar to ribosomal protein S23 [R. norvegicus] EST
GAGGTCAGTG 4 8 3.4 0.039 None Novel tag Nov
TCTGGGTCAT 4 8 3.4 0.039 2633 Isocitrate dehydrogenase 3 (NAD+) alpha (Idh3a) Met
TGCTGCTGCC 5 10 3.4 0.021 3850 ESTs, moderately similar to C chain C, human glyoxalase I complexed with S-P-nitrobenzyloxycarbonylglutathione[H. sapiens] EST
ACGCAATAAA 11 21 3.2 0.001 19158 ESTs, highly similar to PUA1_mouse adenylosuccinate synthetase, muscle isozyme (IMP–aspartate ligase) (ADSS) (AMPSASE) [M. musculus] EST
CACATCTGGT 6 11 3.1 0.021 11088 Heat shock 70kD protein 5 (Hspa5) Pro
TGGCACTATC 17 31 3.1 1.2E-04 7279 ESTs EST
TTGAAATCAA 6 11 3.1 0.021 22882 NADH ubiquinone oxidoreductase subunit B13 Met
86600 ESTs, highly similar to vacuolar protein sorting 29 (S. pombe); vacuolar protein sorting 29 (yeast); vacuolar sorting protein 29 [M. musculus]
GCCAAGCCAT 5 9 3.0 0.040 36770 ESTs, weakly similar to CLK3_RAT protein kinase CLK3(CDC-like kinase 3) [R. norvegicus] EST
TAACGCTGTT 5 9 3.0 0.040 19224 ESTs, weakly similar to solute carrier family 25 (carnitine/acylcarnitine translocase), member 20[R. norvegicus] EST
ACATTTCCCC 15 3 −3.0 0.047 8524 ESTs, highly similar to putative protein kinase C inhibitor[R. norvegicus] EST
CCTAGCCCCT 15 3 −3.0 0.047 7961 ESTs, weakly similar to transforming growth factor-beta (TGF-beta) masking protein large subunit [R. norvegicus] EST
CCTTTAATAA 15 3 −3.0 0.047 8405 ESTs, highly similar to CRP1_MOUSE cysteine-rich protein 1 (Cysteine-rich intestinal protein) (CRIP) [R. norvegicus] EST
TGGGTTGCTA 15 3 −3.0 0.047 None Novel tag Nov
CCCGTGTGCT 16 3 −3.2 0.034 3381 Ribosomal protein S9 (Rps9) Pro
ATTCTGATGA 23 4 −3.4 0.009 9448 ESTs EST
TGGTGCCTCT 23 4 −3.4 0.009 3061 Fatty acid coenzyme A ligase, long chain 5 (Facl5) Met, Lip
AACACTACGG 6 0 −3.6 0.046 4120 ESTs, weakly similar to S11349 nonhistone chromosomal protein HMG-17 EST
AAGAAAGGAG 6 0 −3.6 0.046 2910 Procollagen C-proteinase enhancer protein (Pcolce) CS/ECM
(continues)
Table 1D.
 
(continued). Differentially Regulated Transcripts in Dark-Reared Rat EOM
Table 1D.
 
(continued). Differentially Regulated Transcripts in Dark-Reared Rat EOM
Tag LR DR DR/LR P Unigene (RS) Gene Name Function
ACGCCCTTCA 6 0 −3.6 0.046 3292 ESTs, moderately similar to mitochondrial ribosomal protein S17 [M. musculus] EST
ACTACCGGGC 6 0 −3.6 0.046 37686 ESTs, moderately similar to S11276 alpha-adaptin c EST
AGGTCCTTGT 6 0 −3.6 0.046 None Novel tag Nov
CACGCCTTTC 6 0 −3.6 0.046 9215 Acetoacetyl-CoA synthetase (Hba1) Met, Lip
CACGCCTTTC 6 0 −3.6 0.046 11229 Hemoglobin, alpha 1 (Hba1) Oth
CATTGCGTGG 6 0 −3.6 0.046 2880 ESTs EST
CCCTGGTCAC 6 0 −3.6 0.046 None Novel tag Nov
CGCGGAGGCC 6 0 −3.6 0.046 11207 Thrombospondin 4 (Thbs4) CS/ECM
CGTGGATCCC 6 0 −3.6 0.046 12256 ESTs, moderately similar to CDNC_MOUSECYCLIN-DEPENDENT KINASE INHIBITOR 1C(CYCLIN-DEPENDENT KINASE INHIBITOR P57)(P57KIP2) [M. musculus] EST
CTTCAGCTAT 6 0 −3.6 0.046 22479 ESTs EST
GAAAGAAACT 6 0 −3.6 0.046 31991 Secreted acidic cystein-rich glycoprotein (osteonectin) C/D
GAACAATGGA 6 0 −3.6 0.046 8706 pR-ET2 encoded oncodevelopmental protein Imm
GACCAACAGA 6 0 −3.6 0.046 2953 Collagen, type 1, alpha 1 (Colla1) CS/ECM
GATATCAACT 6 0 −3.6 0.046 None Novel tag Nov
GATTCCCCCC 6 0 −3.6 0.046 16597 ESTs EST
GATTCTTCAG 6 0 −3.6 0.046 7262 Defender against cell death 1 C/D
GCACCGGGAA 6 0 −3.6 0.046 None Novel tag Nov
GCATATTTGA 6 0 −3.6 0.046 2026 ESTs, moderately similar to cytochrome c oxidase subunit VIIb; 1100001F07Rik [M. musculus] EST
GCTTTGGCTT 6 0 −3.6 0.046 31976 Branched chain keto acid dehydrogenase kinase (Bekdk) Met, Lip
GTTTCCCCTC 6 0 −3.6 0.046 None Novel tag Nov
TAAATTGTAG 6 0 −3.6 0.046 None Novel tag Nov
TCCCCTACAT 6 0 −3.6 0.046 None Novel tag Nov
TCCTCAGCAC 6 0 −3.6 0.046 6120 ESTs, highly similar to C54819 actin-capping protein beta chain, splice form 2 EST
TGATTCGGTT 6 0 −3.6 0.046 40162 ESTs EST
TGGACTGCTG 6 0 −3.6 0.046 11301 Mannosidase, alpha, class 2C, member (Man2c1) Oth
TGGCCAGGGC 6 0 −3.6 0.046 None Novel tag Nov
TGGGCCCCTG 6 0 −3.6 0.046 None Novel tag Nov
TTCAACCTCA 6 0 −3.6 0.046 16833 ESTs, weakly similar to ROD_RAT; heterogeneous nuclear ribonucleoprotein D0 (hnRNP D0; AU-rich element RNA-binding protein 1) [R. norvegicus] EST
TTTGGGAAAA 6 0 −3.6 0.046 52763 Ankyrin 3 (G) Cyto
TTTTTACTGA 6 0 −3.6 0.046 8450 ESTs, highly similar to integral membrane protein 3[M. musculus] EST
AAATAAAGAT 25 4 −3.7 0.005 4958 Sodium channel, voltage-gated, type 1, beta polypeptide (Scn1b) Rec
65438 ESTs
AAGACAGCTG 19 3 −3.8 0.013 39743 RT1 class Ib gene (RT1-R) Imm
37183 ESTs
83611 MHC class I RT1.O type 149 processed pseudogene
ACAGTGGGGA 13 2 −3.8 0.037 22995 ESTs, highly similar to pleckstrin 2 [M. musculus] EST
GTGTTCTATA 32 5 −3.8 0.001 None Novel tag Nov
CTTTATTCCA 33 5 −3.9 0.001 2953 Collagen, type 1, alpha 1 (Collal) CS/ECM
TCTTCTCACA 20 3 −3.9 0.009 6172 Ribosomal protein L39 (Rpl39) Pro
AAATGCTTGG 7 0 −4.1 0.029 74273 ESTs, weakly similar to S11661 talin EST
AAGTCCTTTT 7 0 −4.1 0.029 6211 Glucocorticoid-induced leucine zipper (Gilz) Trans
35608 ESTs
AATGGGAGGC 7 0 −4.1 0.029 None Novel tag Nov
ACCCCCAGTC 14 2 −4.1 0.026 81140 Thyroid hormone responsive protein (spot14) (Thrsp) Met, Lip
AGATGTATTT 7 0 −4.1 0.029 4178 ESTs, highly similar to RIKEN cDNA 1010001C05[M. musculus] EST
AGGCTGGTGA 7 0 −4.1 0.029 6016 Proteasome (prosome, macropain) subunit, beta type 1 (Psmb1) Imm, Pro
25100 ESTs
ATAACAACAT 7 0 −4.1 0.029 81261 EST EST
ATACACATAA 35 5 −4.1 4.3E-04 None Novel tag Nov
ATGAAGCCAG 14 2 −4.1 0.026 54594 Voltage-dependent anion channel 1 (Vdac1) Rec
ATGTAGCCAG 7 0 −4.1 0.029 20160 tRNA selenocysteine associated protein Pro
CAAACAATCA 7 0 −4.1 0.029 None Novel tag Nov
CACGGCCTCT 7 0 −4.1 0.029 None Novel tag Nov
CATTCGGAGA 7 0 −4.1 0.029 None Novel tag Nov
CCCAGCACTT 7 0 −4.1 0.029 22230 ESTs EST
GATCAAGTCA 7 0 −4.1 0.029 None Novel tag Nov
(continues)
Table 1E.
 
(continued). Differentially Regulated Transcripts in Dark-Reared Rat EOM
Table 1E.
 
(continued). Differentially Regulated Transcripts in Dark-Reared Rat EOM
Tag LR DR DR/LR P Unigene (RS) Gene Name Function
GCAATTATTG 7 0 −4.1 0.029 9197 ESTs EST
GCCGCAAAGG 7 0 −4.1 0.029 None Novel tag Nov
GGCAGAAACT 7 0 −4.1 0.029 None Novel tag Nov
GGGATGGACG 7 0 −4.1 0.029 30176 Complement component 4 Imm
TAGGCCACCC 7 0 −4.1 0.029 None Novel tag Nov
TAGGTGTGGG 7 0 −4.1 0.029 871 Calponin 3, acidic (Cnn3) Cyto, Mus
28172 ESTs
TCTATTCTCA 14 2 −4.1 0.026 None Novel tag Nov
GCTTCTCAGT 23 3 −4.5 0.003 11004 Phosphofructokinase, muscle (Pfkm) Met
AATCGAAGGC 8 0 −4.7 0.018 None Novel tag Nov
ATACCCATAA 8 0 −4.7 0.018 None Novel tag Nov
ATTTATTACA 8 0 −4.7 0.018 None Novel tag Nov
CCCTGAGTCC 24 3 −4.7 0.002 69 Ribosomal protein L14 Pro
CGCAAGGCCC 8 0 −4.7 0.018 49290 ESTs, highly similar to HTGN29 protein [H. sapiens] EST
GACACCTTGA 8 0 −4.7 0.018 35336 ESTs, weakly similar to hypothetical protein FLJ20559[H. sapiens] EST
GATCCCCCCA 8 0 −4.7 0.018 None Novel tag Nov
GCACTAGCTG 8 0 −4.7 0.018 37311 Progesterone receptor membrane component 1 (Pgrmc1) Rec
GCGCCCTGAG 8 0 −4.7 0.018 None Novel tag Nov
ACTCGGATGC 33 4 −4.9 2.8E-04 18013 ESTs, moderately similar to RIKEN cDNA 1810011O01[R. norvegicus] EST
AGCACAGTTA 33 4 −4.9 2.8E-04 13092 ESTs, weakly similar to RET1_RAT retinol-binding protein I; cellular (Cellular retinol-binding protein; CRBP)[R. norvegicus] EST
AGGTCCACCA 9 0 −5.3 0.011 None Novel tag Nov
ATACTGCACT 18 2 −5.3 0.006 None Novel tag Nov
ATACTGCCAC 9 0 −5.3 0.011 None Novel tag Nov
GCCTCCAAGA 9 0 −5.3 0.011 1002 Plasminogen activator, tissue (Plat) CS/ECM
GCGGTGGCAG 9 0 −5.3 0.011 38807 ESTs EST
GGTGAGGTTT 9 0 −5.3 0.011 3870 ESTs, moderately similar to hypothetical protein MNCb-0169 [M. musculus] EST
TGAGGTCTTG 9 0 −5.3 0.011 8476 ESTs EST
CAGCTCTGGG 10 1 −5.9 0.036 15228 ESTs, highly similar to toll-associated serine protease[M. musculus] EST
CTCCGAGAGG 10 1 −5.9 0.036 4287 ESTs, weakly similar to A43932 mucin 2 precursor, intestinal EST
CTCTCTAAAC 10 1 −5.9 0.036 947 ESTs, weakly similar to B26423 serin proteinase inhibitor 2.2 EST
GATGTGACCA 10 1 −5.9 0.036 125 ESTs, highly similar to eukaryotic translation initiation factor 3, subunit 2 (beta, 36kD); TGF-beta receptor binding protein; DNA segment, Chr 4, ERATO Doi 632, expressed [M. musculus] EST
TAGGTACAGC 10 0 −5.9 0.007 None Novel tag Nov
TCTGAATCTT 10 0 −5.9 0.007 None Novel tag Nov
TTATTTGGTG 10 1 −5.9 0.036 34356 ThyM.cell surface antigen Imm, CS/ECM
AAAACACATA 11 1 −6.5 0.024 None Novel tag Nov
GCCTCTGCTG 11 1 −6.5 0.024 3777 ESTs, moderately similar to RIKEN cDNA 2310040G17; expressed sequence AI425883 [M. musculus] EST
AATGCCCCCC 71 6 −7.0 2.7E-09 None Novel tag Nov
AAACTGACAC 12 1 −7.1 0.016 None Novel tag Nov
CTGAAAAAAA 12 1 −7.1 0.016 81140 Thyroid hormone responsive protein (spot14) (Thrsp) Met, Lip
6510 ESTs, highly similar to mannosidase, beta A, lysosomal-like[H. sapiens]
GCTCCCAGGG 12 1 −7.1 0.016 23659 ESTs EST
GGGTCAACTG 12 0 −7.1 0.003 4083 S-100 related protein, clone 42C (S100a10) Sig, C/D
TTTGGGAGAA 12 0 −7.1 0.003 None Novel tag Nov
CTGGAGCATC 13 1 −7.7 0.011 68036 ESTs EST
ATAACCCATA 14 1 −8.3 0.007 None Novel tag Nov
ATACCACATA 14 1 −8.3 0.007 None Novel tag Nov
ATATTGACAC 15 1 −8.9 0.005 None Novel tag Nov
ATAACACAAT 16 0 −9.5 4.4E-04 None Novel tag Nov
CCCTGAGCGG 17 1 −10.1 0.002 2514 Transferrin (Tf) Rec
ATACTTGACA 61 3 −12.0 8.9E-10 25364 ESTs EST
Table 2.
 
Differentially Regulated Transcripts in Monocularly Deprived Monkey Lateral Rectus
Table 2.
 
Differentially Regulated Transcripts in Monocularly Deprived Monkey Lateral Rectus
GenBank Acc. No. Gene Name Symbol Change (×) Function
NM_018563 Hypothetical protein PR00758 PRO0758 48.5 Unknown
AF094508 Dentin sialophosphoprotein DSPP 4.1 Extracellular matrix
NM_015978 Putative protein-tyrosine kinase LOC51086 2.7 Unknown
NM_025012 Hypothetical protein FLJ13769; FLJ13769 2.4 Unknown
BG252666 ATPase, Class I, type 8B; member 1 ATP8B1 2.3 Aminophospholipid transport
NM_000393 Collagen, type V, alpha 2 COL5A2 −1.8 Extracellular matrix
AU144167 Collagen, type III, alpha 1 (Ehlers-Danlos syndrome type IV; autosomal dominant) COL3A1 −1.8 Extracellular matrix
NM_002048 Growth arrest-specific 1 GAS1 −1.9 Cell proliferation and growth
NM_000089 Collagen, type I, alpha 2 COL1A2 −1.9 Extracellular matrix
M97935 Signal transducer and activator of transcription 1, 91kDa STAT1 −2.0 Signal transduction; cell proliferation and growth
NM_000088 Collagen, type I, alpha 1 COL1A1 −2.0 Extracellular matrix
AF138300 Decorin DCN −2.1 Extracellular matrix
AF130082 Hypothetical protein PRO3121 PRO3121 −2.1 Unknown
AV753392 Heterogeneous nuclear ribonucleoprotein HNRPH1 −2.2 RNA processing
AF138302 Decorin DCN −2.3 Extracellular matrix
BF514079 cDNA FLJ38575 fis, clone HCHON2007046, mRNA sequence −2.4 Unknown
NM_002065 Glutamate-ammonia ligase (glutamine synthase) GLUL −2.7 Amino acid metabolism and NO biosynthesis
A1813758 Collagen, type III, alpha 1 (Ehlers-Danlos syndrome type IV, autosomal dominant) COL3A1 −2.7 Extracellular matrix
NM_002612 Pyruvate dehydrogenase kinase, isoenzyme 4 PDK4 −4.7 Glycolysis
NM_022831 Hypothetical protein FLJ12806 FLJ12806 −7.9 Unknown
Table 3.
 
Differentially Regulated Transcripts in Monocularly Deprived Monkey Medial Rectus
Table 3.
 
Differentially Regulated Transcripts in Monocularly Deprived Monkey Medial Rectus
GenBank Acc. No. Gene Name Symbol Change (×) Function
L12711 Transketolase (Wernicke-Korsakoff syndrome) TKT 7.1 Pentose phosphate pathway
U63131 CDC37 cell division cycle 37 homologue S. cerevisiae) CDC37 3.6 Cell cycle regulation; cell proliferation and growth
J03068 N-acylaminoacyl-peptide hydrolase APEH 2.8 Amino acid metabolism
NM_000703 ATPase, Na+/K+ transporting, alpha 3 polypeptide ATP1A3 2.8 Cation transport
NM_001540 Heat shock 27kD protein 1 HSPB1 2.7 Protein modification; stress response
NM_002541 Oxoglutarate (alpha-ketoglutarate) dehydrogenase (lipoamide) OGDH 2.3 Energy metabolism
NM_002869 RAB6A, member RAS oncogene family RAB6A 2.3 GTPase; membrane transport
AF172268 KIAA0551 protein KIAA0551 2.1 Unknown
NM_002397 MADS box transcription enhancer factor 2, polypeptide C (myocyte enhancer factor 2C) MEF2C 1.9 Myogenesis
NM_005729 Peptidylprolyl isomerase F (cyclophilin F) PPIF 1.9 Protein modification
NM_005952 Metallothionein IX MTIX −1.8 Heavy metal binding
BC001971 Cyclin-dependent kinase inhibitor 1B (p27, Kip1) CDKN1B −1.8 Cell cycle regulation; cell proliferation and growth
NM_001186 BTB and CNC homology 1, basic leucine zipper transcription factor 1 BACH1 −1.8 Transcription
AL161952 Glutamate-ammonia ligase (glutamine synthase) GLUL −1.9 Amino acid metabolism
NM_001855 Collagen, type XV, alpha 1 COL15A1 −1.9 Extracellular matrix
M83772 Flavin-containing monooxygenase 3 FMO3 −1.9 Microsome
BF791738 Hypothetical protein PRO2751 PRO2751 −2.0 Unknown
AF153330 Solute carrier family 19 (thiamin transporter), member 2 SLC19A2 −2.1 Transporter
NM_000161 GTP cyclohydrolase 1 (dopa-responsive dystonia) GCH1 −2.1 Amino acid metabolism; biosynthesis of NO
BF514079 cDNA FLJ38575 fis, clone HCHON2007046, mRNA sequence −2.4 Unknown
The authors thank Xiaohua Zhou, Sriram Kasturi, Anita Merriam, Patrick Leahy, Francisco Andrade, and Bendi Gong for technical support. 
Hubel, DH, Wiesel, TN. (1965) Binocular interaction in striate cortex of kittens reared with artificial squint J Neurophysiol 28,1041-1059 [PubMed]
Hubel, DH, Wiesel, TN. (1970) The period of susceptibility to the physiological effects of unilateral eye closure in kittens J Physiol 206,419-436 [CrossRef] [PubMed]
Collewijn, H. (1977) Eye and head movements in freely moving rabbits J Physiol 266,471-498 [CrossRef] [PubMed]
Dell’Osso, LF, Williams, RW. (1995) Ocular motor abnormalities in achiasmatic mutant Belgian sheepdogs: unyoked eye movements in a mammal Vision Res 35,109-116 [CrossRef] [PubMed]
Kiorpes, L, Walton, PJ, O’Keefe, LP, Movshon, JA, Lisberger, SG. (1996) Effects of early-onset artificial strabismus on pursuit eye movements and on neuronal responses in area MT of macaque monkeys J Neurosci 16,6537-6553 [PubMed]
Rothblat, LA, Schwartz, ML, Kasdan, PM. (1978) Monocular deprivation in the rat: evidence for an age-related defect in visual behavior Brain Res 158,456-460 [CrossRef] [PubMed]
Sparks, DL, Mays, LE, Gurski, MR, Hickey, TL. (1986) Long- and short-term monocular deprivation in the rhesus monkey: effects on visual fields and optokinetic nystagmus J Neurosci 6,1771-1780 [PubMed]
Tychsen, L, Hurtig, RR, Scott, WE. (1985) Pursuit is impaired but the vestibulo-ocular reflex is normal in infantile strabismus Arch Ophthalmol 103,536-539 [CrossRef] [PubMed]
van Hof-Van Duin, J. (1976) Development of visuomotor behavior in normal and dark-reared cats Brain Res 104,233-241 [CrossRef] [PubMed]
Cynader, M, Harris, L. (1980) Eye movement in strabismic cats Nature 286,64-65 [CrossRef] [PubMed]
Catz, DS, Fischer, LM, Kelley, DB. (1995) Androgen regulation of a laryngeal-specific myosin heavy chain mRNA isoform whose expression is sexually differentiated Dev Biol 171,448-457 [CrossRef] [PubMed]
Hoh, JF, Hughes, S, Hoy, JF. (1988) Myogenic and neurogenic regulation of myosin gene expression in cat jaw-closing muscles regenerating in fast and slow limb muscle beds J Muscle Res Cell Motil 9,59-72 [CrossRef] [PubMed]
Liu, ZJ, Ikeda, K, Harada, S, Kasahara, Y, Ito, G. (1998) Functional properties of jaw and tongue muscles in rats fed a liquid diet after being weaned J Dent Res 77,366-376 [CrossRef] [PubMed]
Edwards, CJ, Yamamoto, K, Kikuyama, S, Kelley, DB. (1999) Prolactin opens the sensitive period for androgen regulation of a larynx-specific myosin heavy chain gene J Neurobiol 41,443-451 [CrossRef] [PubMed]
Cheng, G, Porter, JD. (2002) Transcriptional profile of rat extraocular muscle by serial analysis of gene expression Invest Ophthalmol Vis Sci 43,1048-1058 [PubMed]
Porter, JD, Baker, RS. (1996) Muscles of a different “color”: the unusual properties of the extraocular muscles may predispose or protect them in neurogenic and myogenic disease Neurology 46,30-37 [CrossRef] [PubMed]
Porter, JD, Khanna, S, Kaminski, HJ, et al (2001) Extraocular muscle is defined by a fundamentally distinct gene expression profile Proc Natl Acad Sci USA 98,12062-12067 [CrossRef] [PubMed]
Fischer, MD, Gorospe, JR, Felder, E, et al (2002) Expression profiling reveals metabolic and structural components of extraocular muscles Physiol Genomics 9,71-84 [CrossRef] [PubMed]
Khanna, S, Merriam, AP, Gong, B, Leahy, P, Porter, JD. () Comprehensive expression profiling by muscle tissue class and identification of the molecular niche of extraocular muscle FASEB J In press
Porter, JD, Hauser, KF. (1993) Survival of extraocular muscle in long-term organotypic culture: differential influence of appropriate and inappropriate motoneurons Dev Biol 160,39-50 [CrossRef] [PubMed]
Porter, JD, Baker, RS. (1992) Prenatal morphogenesis of primate extraocular muscle: neuromuscular junction formation and fiber type differentiation Invest Ophthalmol Vis Sci 33,657-670 [PubMed]
Porter, JD, Karathanasis, P. (1999) The development of extraocular muscle calcium homeostasis parallels visuomotor system maturation Biochem Biophys Res Commun 257,678-683 [CrossRef] [PubMed]
Porter, JD, Merriam, AP, Gong, B, et al () Postnatal suppression of myomesin, muscle creatine kinase, and the M-line in rat extraocular muscle J Exp Biol In press
Brueckner, JK, Itkis, O, Porter, JD. (1996) Spatial and temporal patterns of myosin heavy chain expression in developing rat extraocular muscle J Muscle Res Cell Motil 17,297-312 [PubMed]
Kerns, JM, Rothblat, LA. (1981) The effects of monocular deprivation on the development of the rat trochlear nerve Brain Res 230,367-371 [CrossRef] [PubMed]
Lennerstrand, G, Hanson, J. (1979) Contractile properties of extraocular muscle in cats reared with monocular lid closure and artificial squint Acta Ophthalmol 57,591-599
Lennerstrand, G. (1979) Contractile properties of extraocular muscle in Siamese cat Acta Ophthalmol 57,1030-1038
Lennerstrand, G. (1980) Histochemical studies on the inferior oblique muscle of Siamese cats and domestic cats with unilateral lid suture Exp Eye Res 30,619-639 [CrossRef] [PubMed]
Brueckner, JK, Porter, JD. (1998) Visual system maldevelopment disrupts extraocular muscle-specific myosin expression J Appl Physiol 85,584-592 [PubMed]
Brueckner, JK, Ashby, LP, Prichard, JR, Porter, JD. (1999) Vestibulo-ocular pathways modulate extraocular muscle myosin expression patterns Cell Tissue Res 295,477-484 [CrossRef] [PubMed]
Porter, JD, Leahy, P, Khanna, S, Cheng, G, Veigl, ML. (2003) Applicability and practice of genome-wide expression profiling: insights from studies of skeletal muscle diversity and disease mechanisms Appasani, K eds. Perspectives in Gene Expression ,221-244 Eaton Publishing Westboro, MA.
Davson, H. (1990) Physiology of the Eye Pergammon Press Elmsfield, NY.
Boothe, RG, Fulton, AB. (2000) Amblyopia Albert, DM Jakobiec, FA eds. Principals and Practice of Ophthalmology ,4340-4358 WB Saunders Co. Philadelphia.
Datson, NA, van der Perk-de Jong, J, van den Berg, MP, de Kloet, ER, Vreugdenhil, E. (1999) MicroSAGE: a modified procedure for serial analysis of gene expression in limited amounts of tissue Nucleic Acids Res 27,1300-1307 [CrossRef] [PubMed]
Margulies, EH, Innis, JW. (2000) eSAGE: managing and analysing data generated with serial analysis of gene expression (SAGE) Bioinformatics 16,650-651 [CrossRef] [PubMed]
Audic, S, Claverie, JM. (1997) The significance of digital gene expression profiles Genome Res 7,986-995 [PubMed]
Porter, JD, Khanna, S, Kaminski, HJ, et al (2002) A chronic inflammatory response dominates the skeletal muscle molecular signature in dystrophin-deficient mdx mice Hum Mol Genet 11,263-272 [CrossRef] [PubMed]
Enard, W, Khaitovich, P, Klose, J, et al (2002) Intra- and interspecific variation in primate gene expression patterns Science 296,340-343 [CrossRef] [PubMed]
Velculescu, VE, Zhang, L, Zhou, W, et al (1997) Characterization of the yeast transcriptome Cell 88,243-251 [CrossRef] [PubMed]
Briggs, MM, Schachat, F. (2002) The superfast extraocular myosin (MYH13) is localized to the innervation zone in both the global and orbital layers of rabbit extraocular muscle J Exp Biol 205,3133-3142 [PubMed]
Rubinstein, NA, Hoh, JF. (2000) The distribution of myosin heavy chain isoforms among rat extraocular muscle fiber types Invest Ophthalmol Vis Sci 41,3391-3398 [PubMed]
Wieczorek, DF, Periasamy, M, Butler-Browne, GS, Whalen, RG, Nadal-Ginard, B. (1985) Co-expression of multiple myosin heavy chain genes, in addition to a tissue-specific one, in extraocular musculature J Cell Biol 101,618-629 [CrossRef] [PubMed]
Andrade, FH, Merriam, AP, Porter, JD. (2002) Extraocular muscle gene expression and function after dark rearing Ann NY Acad Sci 956,391-393 [CrossRef] [PubMed]
Porter, JD, Baker, RF. (1993) Developmental adaptations in the extraocular muscles of Macaca nemestrina may reflect a predisposition to strabismus Strabismus 1,173-180 [CrossRef] [PubMed]
Figure 1.
 
Frequency distribution histograms of SAGE tags derived from DR rat EOM. (A) Semilog plot of the frequency of SAGE tags detected at specific abundance levels. Matched tags are those that are represented in genomics databases as known genes or ESTs. Novel tags represent mRNA sequences not found in these databases. Novel tags were most abundant among the single-copy group and declined as a percentage of all tags with increasing copy number. (B) Plot showing the frequency of matched tags among tag abundance groups.
Figure 1.
 
Frequency distribution histograms of SAGE tags derived from DR rat EOM. (A) Semilog plot of the frequency of SAGE tags detected at specific abundance levels. Matched tags are those that are represented in genomics databases as known genes or ESTs. Novel tags represent mRNA sequences not found in these databases. Novel tags were most abundant among the single-copy group and declined as a percentage of all tags with increasing copy number. (B) Plot showing the frequency of matched tags among tag abundance groups.
Figure 2.
 
Venn diagrams representing SAGE tag distribution patterns in the dark-reared (DR) and light-reared (LR) rat EOM libraries. (A) Distribution between the two libraries when all SAGE tag copy number categories were considered. Note overlap represents only 19.7% of the total number of unique tags. (B) Distribution between the two libraries when SAGE tag copy number was restricted to three copies per tag or more. Overlap between the two libraries was 78%.
Figure 2.
 
Venn diagrams representing SAGE tag distribution patterns in the dark-reared (DR) and light-reared (LR) rat EOM libraries. (A) Distribution between the two libraries when all SAGE tag copy number categories were considered. Note overlap represents only 19.7% of the total number of unique tags. (B) Distribution between the two libraries when SAGE tag copy number was restricted to three copies per tag or more. Overlap between the two libraries was 78%.
Figure 3.
 
Functional category distribution of SAGE tags detected as differentially regulated in DR rat EOM. Top: Functional distribution of all 280 unique tags. Bottom: Functional distribution of the 71 matched tags that have been linked to known genes. Mus, muscle-related; Cyto, cytoskeletal; Met, metabolism/mitochondrial related; Lip, lipid metabolism; CS/ECM, cell surface/extracellular matrix; Sig, signaling/cell–cell communication; C/D, cell proliferation/death; Trans, transcription; Pro, protein synthesis/modification; Rec, receptor/transporter/ion channel; Imm, immune response; Oth, other/unknown.
Figure 3.
 
Functional category distribution of SAGE tags detected as differentially regulated in DR rat EOM. Top: Functional distribution of all 280 unique tags. Bottom: Functional distribution of the 71 matched tags that have been linked to known genes. Mus, muscle-related; Cyto, cytoskeletal; Met, metabolism/mitochondrial related; Lip, lipid metabolism; CS/ECM, cell surface/extracellular matrix; Sig, signaling/cell–cell communication; C/D, cell proliferation/death; Trans, transcription; Pro, protein synthesis/modification; Rec, receptor/transporter/ion channel; Imm, immune response; Oth, other/unknown.
Table 1.
 
Differentially Regulated Transcripts in Dark-Reared Rat EOM
Table 1.
 
Differentially Regulated Transcripts in Dark-Reared Rat EOM
Tag LR DR DR/LR P Unigene (RS) Gene Name Function
TCACTTTCTA 1 11 18.6 1.2E-04 None Novel tag Nov
GCAGTGCAAA 1 9 15.2 0.001 12436 ESTs, highly similar to hypothetical protein; FLJ10055[Homo sapiens] EST
GTGATAGACA 1 9 15.2 0.001 2944 Peroxiredoxin 6 (Prdx6) Oth
TGGGAACTGT 1 9 15.2 0.001 17567 ESTs, weakly similar to FZD2_RAT; Frizzled 2 precursor (Frizzled-2) (Fz-2); (rFz2) [Rattus norvegicus] EST
ACTGACAAAA 0 8 13.5 2.7E-04 12038 ESTs EST
TACATAGCCA 1 8 13.5 0.002 11363 Pyruvate dehydrogenase kinase 2 (Pdk2) Met
CTCCTGCAGT 1 7 11.8 0.004 3682 ESTs, moderately similar to ESTD_HUMAN esterase D[H. sapiens] EST
TGAGCTCTGA 1 7 11.8 0.004 None Novel tag Nov
CAACCCCAAA 1 6 10.1 0.011 6541 ESTs, weakly similar to RP3A_RAT Rabphilin-3A[R. norvegicus] EST
CAGCTATTGT 0 6 10.1 0.002 36855 ESTs, highly similar to JC6161 kinesin-associated protein KAP3 splice form A EST
CATACGCTCA 1 6 10.1 0.011 None Novel tag Nov
CTCGAGCGGC 0 6 10.1 0.002 55376 EST EST
GCACTTGCTG 1 6 10.1 0.011 3996 ESTs, highly similar to OBRG_RAT; leptin receptor gene-related protein (OB-R gene related protein) (OB-RGRP)[R. norvegicus] EST
GCATCAGTAC 0 6 10.1 0.002 16830 ESTs EST
GTGTGGAATC 1 6 10.1 0.011 839 FXYD domain-containing ion transport regulator (Fxyd6) Rec
AAATAAATGT 0 5 8.4 0.005 9668 Myelin-associated glycoprotein (Mag) Oth
8978 ESTs, weakly similar to B34252 acyl-CoA dehydrogenase(EC 1.3.99.3) short-chain-specific precursor, hepatic
CAAAATAGTT 1 5 8.4 0.025 None Novel tag Nov
CAGCAATAAA 3 15 8.4 7.2E-05 15530 ESTs EST
CAGCTATGCA 1 5 8.4 0.025 7258 ESTs, highly similar to male-specific lethal-3 H.log 1 (Drosophila) [Mus musculus] EST
CCCATAATCC 2 10 8.4 0.001 3380 Synaptic glycoprotein SC2 (SC2) Oth
CTATTTAATT 1 5 8.4 0.025 8763 ESTs, weakly similar to TXTP_RAT tricarboxylate transport protein, mitochondrial precursor (Citrate transport protein) (CTP) (Tricarboxylate carrier protein) [R. norvegicus] EST
CTCCTGAAGG 1 5 8.4 0.025 2784 ESTs, highly similar to UB6B_MOUSE; ubiquitin-conjugating enzyme E2-23 kDa; (ubiquitin-protein ligase; ubiquitin carrier protein) [M. musculus] EST
CTTTTTATAC 0 5 8.4 0.005 13643 ESTs, highly similar to calcium binding atopy-related autoantigen 1; atopy-related autoantigen [H. sapiens] EST
1040 ESTs, highly similar to G0S2_MOUSE; putative lymphocyte G0/G1 switch protein 2 (G0S2-like protein) [M. musculus]
GATGCCTCCC 0 5 8.4 0.005 None Novel tag Nov
GCAGAGAATG 1 5 8.4 0.025 4077 ESTs, weakly similar to A34866 T-cell surface protein RT6.2 precursor EST
GCTGGTTCCA 0 5 8.4 0.005 9726 Calpain 3 (Capn3) Mus
GGCTACGGTT 1 5 8.4 0.025 None Novel tag Nov
GGGCTGCCCA 1 5 8.4 0.025 3053 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member2 Oth
38063 ESTs, weakly similar to sugar transporter[Caenorhabditis elegans] EST
GTAGGAAGAT 0 5 8.4 0.005 33378 ESTs, highly similar to feminization 1 H.log a (C. elegans); feminization 1 a H.log [C. elegans; M. musculus] EST
GTTTCGTGGT 1 5 8.4 0.025 17086 ESTs EST
TACCCCTTTA 1 5 8.4 0.025 None Novel tag Nov
TCACCTTGTT 1 5 8.4 0.025 31796 Acyl-coA oxidase (Acoal) Met, Lip
TCCTGGCAGT 1 5 8.4 0.025 None Novel tag Nov
TGAGCAGACG 1 5 8.4 0.025 35504 ESTs EST
TGCCATTGCA 0 5 8.4 0.005 32316 ESTs, weakly similar to sialyltransferase 3; sialyltransferase)[R. norvegicus] EST
TGTTTGCAGA 0 5 8.4 0.005 22183 ESTs, moderately similar to hypothetical protein dJ12208.2[H. sapiens] EST
TTCACAAAGG 0 5 8.4 0.005 1276 Proteasome (prosome, macropain) subunit, alpha type 5 (Psma5) Pro
85470 ESTs, weakly similar to JX0229 multicatalytic endopeptidase complex (EC 3.4.99.46) zeta chain
TTGGAATCCA 0 5 8.4 0.005 20119 ESTs EST
TTTTGAGGAC 0 5 8.4 0.005 3496 ESTs EST
ATACTGACAT 2 9 7.6 0.003 None Novel tag Nov
(continues)
Table 1A.
 
(continued). Differentially Regulated Transcripts in Dark-Reared Rat EOM
Table 1A.
 
(continued). Differentially Regulated Transcripts in Dark-Reared Rat EOM
Tag LR DR DR/LR P Unigene (RS) Gene Name Function
AAAAAAGAAA 0 4 6.8 0.014 19930 ESTs, moderately similar to RIKEN cDNA 2310079N02[M. musculus] EST
AAGGTCTTTA 0 4 6.8 0.014 13244 ESTs EST
ACCATCCCTT 0 4 6.8 0.014 None Novel tag Nov
ATAAAACCAG 0 4 6.8 0.014 None Novel tag Nov
CACAAGCGGT 0 4 6.8 0.014 None Novel tag Nov
CCCCCAATTC 0 4 6.8 0.014 31977 Vesicle-associated membrane protein 2 (Vamp2) Oth
6430 ESTs
3748 ESTs, highly similar to gamma tubulin complex component; KIAA1669 protein; similar to Xenopus gamma tubulin interacting protein (yeast SPC98 H.log) [H. sapiens]
CTGAGGGAGG 0 4 6.8 0.014 24472 ESTs, weakly similar to hypothetical protein MGC13119[H. sapiens] EST
CTGATCCAGT 0 4 6.8 0.014 11946 Ubiquitin fusion degradation I-like Pro
GAAGTTGTGC 0 4 6.8 0.014 12833 ESTs, highly similar to T43442 hypothetical protein DKFZp43p1514 EST
GCAACCAAAA 0 4 6.8 0.014 37542 Suppressor of K+ transport defect 3 Oth
GCTGTTCTGT 0 4 6.8 0.014 3628 Glutamate oxaloacetate transaminase 2; mitochondrial (aspartate aminotransferase 2) (Got2) Met
GGCGGGTGGA 0 4 6.8 0.014 20220 ESTs EST
GTATGCCCCC 0 4 6.8 0.014 None Novel tag Nov
GTCCAAGATT 0 4 6.8 0.014 72495 ESTs EST
GTGATGCCAC 0 4 6.8 0.014 22278 ESTs, highly similar to CGE0_HUMAN; protein CGI-140 (protein PTD008) [H. sapiens] EST
GTGCTAACAA 0 4 6.8 0.014 44114 ESTs, highly similar to AT10_MOUSE ADAMTS-10(a disintegrin and metalloproteinase with thrombospondin motifs 10; ADAM-TS 10, ADAM-TS10) [M. musculus] EST
GTTAGGTAGG 0 4 6.8 0.014 3421 Adenylate kinase 2 (Ak2) Met
TAACCAATCA 0 4 6.8 0.014 3548 ESTs, highly similar to small GTP-binding protein rab5[R. norvegicus] EST
TAGGCCACCA 0 4 6.8 0.014 None Novel tag Nov
TATGTGGAAT 0 4 6.8 0.014 7983 ESTs, highly similar to catenin alpha-like 1; alpha-catenin related protein [M. musculus] EST
TGCCAAGCCC 0 4 6.8 0.014 19513 ESTs EST
TGGATCTGAG 0 4 6.8 0.014 72471 ESTs EST
TGTGACAGTG 0 4 6.8 0.014 13976 ESTs EST
TTAATTCATT 2 8 6.8 0.007 2230 Translocase of inner mitochondrial membrane 23 H.log(yeast; Timm23) Met
GACGCCCCCC 3 11 6.2 0.002 None Novel tag Nov
CTGTGCTCGA 2 7 5.9 0.015 26731 ESTs EST
GGAAGTCAGG 2 7 5.9 0.015 None Novel tag Nov
GCGAAAGAAT 3 10 5.6 0.004 6847 Enoyl Coenzyme A hydratase, short chain 1 (Echs1) Met, Lip
GCCCCGGTGC 4 13 5.5 0.001 38221 ESTs, highly similar to cardiac abnormality/abnormal facies (CATCH22); microdeletion syndrome [M. musculus] EST
AAAATCAAGT 0 3 5.1 0.038 19102 ESTs, weakly similar to S21976; probable RNA-directed DNA polymerase (EC 2.7.7.49; clone MH2C) EST
AAGGAAATAA 2 6 5.1 0.032 29754 Prohibitin C/D
ACAGACACTT 0 3 5.1 0.038 8129 ESTs EST
ACATCGTGCG 0 3 5.1 0.038 53919 ESTs, highly similar to human SLC21A6 EST
ACCGTTATAA 0 3 5.1 0.038 1722 Lysosomal-associated membrane protein 2 (Lamp2) Oth
AGAGAAGGGT 0 3 5.1 0.038 44362 Inositol 1,4,5-trisphosphate 3-kinase B (ltpkb) Sig
AGGGAGCCGC 0 3 5.1 0.038 None Novel tag Nov
ATAAGCACAT 0 3 5.1 0.038 None Novel tag Nov
ATAAGTCATA 0 3 5.1 0.038 None Novel tag Nov
ATGATTTAAC 0 3 5.1 0.038 41151 ESTs EST
ATGGGTGGAA 0 3 5.1 0.038 36164 ESTs, highly similar to hypothetical protein FLJ20211[H. sapiens] EST
ATGTGTATGT 0 3 5.1 0.038 2560 ESTs EST
CAAAGACAAT 0 3 5.1 0.038 40403 ESTs, highly similar to HSPC038 protein [H. sapiens] EST
CATAACACAT 0 3 5.1 0.038 None Novel tag Nov
CCGGGGTGAT 0 3 5.1 0.038 None Novel tag Nov
CTATGTAGAC 0 3 5.1 0.038 23858 ESTs, moderately similar to HCDI protein [H. sapiens] EST
CTGCTGTAAT 0 3 5.1 0.038 55106 Glutamate dehydrogenase (Glud1) Oth
CTGTGTGATC 2 6 5.1 0.032 22047 ESTs, moderately similar to T46271 hypothetical protein DKFZp564P2163.1 EST
CTTCCCACTG 0 3 5.1 0.038 2274 Ubiquitin conjugating enzyme E2I (Ube2i) Pro
CTTGCTTTTT 0 3 5.1 0.038 44161 Lamin A (Lmna) Oth
CTTTGAAAGG 0 3 5.1 0.038 None Novel tag Nov
(continues)
Table 1B.
 
(continued). Differentially Regulated Transcripts in Dark-Reared Rat EOM
Table 1B.
 
(continued). Differentially Regulated Transcripts in Dark-Reared Rat EOM
Tag LR DR DR/LR P Unigene (RS) Gene Name Function
GAAAAGTCGA 0 3 5.1 0.038 20571 ESTs EST
GACACAGAAA 0 3 5.1 0.038 41880 ESTs EST
GAGACTCTAC 0 3 5.1 0.038 9091 ESTs, highly similar to KIAA0710 gene product [H. sapiens] EST
GAGGATGCTG 0 3 5.1 0.038 71588 EST EST
GATAAACACA 0 3 5.1 0.038 43517 ESTs EST
GATCACCTGT 2 6 5.1 0.032 17012 ESTs, highly similar to MGPI_MOUSE Microfibril-associated glycoprotein precursor (MAGP) (MAGP-1) [M. musculus] EST
GATGAGGGTC 0 3 5.1 0.038 18199 ESTs, highly similar to A41784 tumor necrosis factor-alpha-induced protein B12 EST
GATTCTGCCC 0 3 5.1 0.038 41894 ESTs EST
GCACACACAT 0 3 5.1 0.038 None Novel tag Nov
GCACGAACAT 0 3 5.1 0.038 7295 EST EST
GCTGAGACTG 0 3 5.1 0.038 11534 ESTs, highly similar to TYRO protein tyrosine kinase binding protein; killer cell activating receptor associated protein[M. musculus] EST
GGACACCAAA 3 9 5.1 0.008 2938 Mitochondrial ribosomal protein L 17 Pro
GGAGTAGATT 0 3 5.1 0.038 3519 Malic enzyme 1, soluble (Mel) Met, Lip
GGCTATTTTA 0 3 5.1 0.038 3988 EST EST
GGCTCAGCTC 0 3 5.1 0.038 None Novel tag Nov
GGGCCATTAG 3 9 5.1 0.008 58 Afadin (AF-6) Sig, Cyto
GGTCCTACCC 0 3 5.1 0.038 33467 ESTs EST
GTCGCTTCTG 0 3 5.1 0.038 6199 ESTs, moderately similar to U2AG_MOUSE Splicing factor U2AF 35 kDa subunit (U2 auxiliary factor 35 kDa subunit) (U2 snRNP auxiliary factor small subunit) [M. musculus] EST
GTGACGGCCT 0 3 5.1 0.038 None Novel tag Nov
GTGCGGGCTC 0 3 5.1 0.038 39333 Endosulfine alpha (Ensa) Rec
GTTTGAGCAT 0 3 5.1 0.038 17490 ESTs EST
TAAAATGTAG 0 3 5.1 0.038 None Novel tag Nov
TAACGTCTAG 0 3 5.1 0.038 59806 EST EST
TAGGTCACAG 0 3 5.1 0.038 None Novel tag Nov
TATTAGTTAT 0 3 5.1 0.038 26749 ESTs EST
TCCAACTTCT 0 3 5.1 0.038 None Novel tag Nov
TCTCTGCCTG 0 3 5.1 0.038 11272 SH3 domain binding protein CR16 Sig
TCTGCCCTCC 0 3 5.1 0.038 25440 ESTs EST
TCTTCTGTGG 0 3 5.1 0.038 3616 ESTs EST
TGAACAAAAA 0 3 5.1 0.038 8839 EST EST
TGACATACGT 0 3 5.1 0.038 7910 ESTs EST
TGATACGATT 0 3 5.1 0.038 3694 ESTs, highly similar to TRAP/Mediator complex component TRAP25 [H. sapiens] EST
TGCACGCGTC 0 3 5.1 0.038 2315 Translin-associated factor X Oth
TGCTGAATCA 0 3 5.1 0.038 25036 ESTs EST
TGGAAAAAAA 0 3 5.1 0.038 35208 ESTs, moderately similar to UCRX_HUMAN ubiquinol-cytochrome C reductase complex 7.2 kDa protein (cytochrome C1, nonheme 7 kDa protein; complex III subunit X; 7.2 kDa cytochrome c1-associated protein subunit; HSPC119) [H. sapiens] EST
TGGGGTCTCA 0 3 5.1 0.038 35476 ESTs EST
TGGGGTTTAT 0 3 5.1 0.038 4107 ESTs EST
TGTGCACCAG 0 3 5.1 0.038 12034 ESTs EST
TGTGTAATGT 0 3 5.1 0.038 758 ESTs, moderately similar to RIKEN cDNA 4833415N24[M. musculus] EST
TGTTTTGGAA 0 3 5.1 0.038 8157 ESTs, highly similar to T08778 hypothetical protein DKFZp58611520.1 EST
TTAAGTGTTG 0 3 5.1 0.038 37781 ESTs, moderately similar to G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein (GIT1) [R. norvegicus] EST
TTCTGCTCCT 0 3 5.1 0.038 21976 ESTs EST
TTGAAGTGGT 0 3 5.1 0.038 73073 ESTs, weakly similar to intersectin (SH3 domain protein 1A) [R. norvegicus] EST
TTGACGGTGG 0 3 5.1 0.038 6834 ESTs EST
TTGATGTTGA 0 3 5.1 0.038 2197 ESTs, moderately similar to erythroblast macrophage protein [M. musculus] EST
TTGTCTGTAA 0 3 5.1 0.038 28239 ESTs EST
TTTAAAGGAA 0 3 5.1 0.038 None Novel tag Nov
TTTACTGGGT 0 3 5.1 0.038 2469 ESTs, highly similar to ZK652.3.p [C. elegans] EST
TTTATAAGTT 0 3 5.1 0.038 17999 ESTs, highly similar to OM40_MOUSE; Probable mitochondrial import receptor subunit TOM40 H.log (translocase of outer membrane 40 kDa subunit H.log) [M. musculus] EST
(continues)
Table 1C.
 
(continued). Differentially Regulated Transcripts in Dark-Reared Rat EOM
Table 1C.
 
(continued). Differentially Regulated Transcripts in Dark-Reared Rat EOM
Tag LR DR DR/LR P Unigene (RS) Gene Name Function
TTTGCATATT 0 3 5.1 0.038 19104 ESTs, weakly similar to ACTB_HUMAN; actin, cytoplasmic 1 (beta-actin) [R. norvegicus] EST
TTTTGAATGC 0 3 5.1 0.038 15531 ESTs EST
CTGAGTGTGG 7 19 4.6 2.2E-04 3902 ESTs, highly similar to B32394 succinate dehydrogenase (ubiquinone) (EC 1.3.5.1) 27K iron-sulfur protein EST
TTAATAAAAG 4 11 4.6 0.005 3393 T-cell activation protein-related (PGR1) Imm
39 ESTs, highly similar to Y184_HUMAN HYPOTHETICAL PROTEIN KIAA0184 [H. sapiens]
CTACACTGGC 3 8 4.5 0.018 41863 Triadin 1 Mus
GGGCACAGGA 3 8 4.5 0.018 7680 ESTs, highly similar to Fas-activated serine/threonine kinase [M. musculus] EST
GTCCCAAGGA 3 8 4.5 0.018 4005 Dodecenoyl-coenzyme A delta isomerase (Dci) Met, Lip
80835 Rat mRNA for delta3, delta2-enoyl-CoA isomerase
GTTCCGACAG 3 8 4.5 0.018 8104 ESTs EST
TGTGGTGGAG 3 8 4.5 0.018 24190 ESTs EST
CAGATCAGAA 5 13 4.4 0.003 14050 ESTs EST
CAGATCTTTG 4 10 4.2 0.010 3761 Ubiquitin C (UBA52) Pro
4300 Ubiquitin A-52 residue ribosomal protein fusion product 1
GACTTGGTCA 4 10 4.2 0.010 None Novel tag Nov
TGGGTTAGAC 5 12 4.1 0.005 919 ESTs, highly similar to prefoldin 1; prefoldin subunit 1[H. sapiens] EST
CTGAGAAATA 3 7 3.9 0.037 8792 ESTs, highly similar to AC48_MOUSE 48; kDa acyl-CoA thioester hydrolase, mitochondrial precursor(p48; Mt-ACT48; protein U8) [M. musculus] EST
GTGAAGAGTT 3 7 3.9 0.037 18515 ESTs, weakly similar to ubiquitin specific protease 2[R. norvegicus] EST
TAAACCAGGT 3 7 3.9 0.037 7349 ESTs EST
TGAAATTTTG 3 7 3.9 0.037 3136 Transaldolase 1 Met, Lip
TAGGGTTACA 4 9 3.8 0.020 28875 Sarcomeric muscle protein (sarcosin) Mus
TTGTGATTAC 4 9 3.8 0.020 21198 MSI Mus
AGCAGAGAAT 5 11 3.7 0.011 4180 ESTs EST
ATACTGACCT 13 27 3.5 1.1E-04 None Novel tag Nov
GTAACACATA 10 21 3.5 0.001 61080 ESTs, weakly similar to JC6197 stromelysin 3 (EC 3.4.24) EST
CAGACCTTGG 5 10 3.4 0.021 3560 Dynein-associated protein RKM23 (Km23) Cyto
CGCTGGGATG 5 10 3.4 0.021 8526 ESTs, weakly similar to ribosomal protein S23 [R. norvegicus] EST
GAGGTCAGTG 4 8 3.4 0.039 None Novel tag Nov
TCTGGGTCAT 4 8 3.4 0.039 2633 Isocitrate dehydrogenase 3 (NAD+) alpha (Idh3a) Met
TGCTGCTGCC 5 10 3.4 0.021 3850 ESTs, moderately similar to C chain C, human glyoxalase I complexed with S-P-nitrobenzyloxycarbonylglutathione[H. sapiens] EST
ACGCAATAAA 11 21 3.2 0.001 19158 ESTs, highly similar to PUA1_mouse adenylosuccinate synthetase, muscle isozyme (IMP–aspartate ligase) (ADSS) (AMPSASE) [M. musculus] EST
CACATCTGGT 6 11 3.1 0.021 11088 Heat shock 70kD protein 5 (Hspa5) Pro
TGGCACTATC 17 31 3.1 1.2E-04 7279 ESTs EST
TTGAAATCAA 6 11 3.1 0.021 22882 NADH ubiquinone oxidoreductase subunit B13 Met
86600 ESTs, highly similar to vacuolar protein sorting 29 (S. pombe); vacuolar protein sorting 29 (yeast); vacuolar sorting protein 29 [M. musculus]
GCCAAGCCAT 5 9 3.0 0.040 36770 ESTs, weakly similar to CLK3_RAT protein kinase CLK3(CDC-like kinase 3) [R. norvegicus] EST
TAACGCTGTT 5 9 3.0 0.040 19224 ESTs, weakly similar to solute carrier family 25 (carnitine/acylcarnitine translocase), member 20[R. norvegicus] EST
ACATTTCCCC 15 3 −3.0 0.047 8524 ESTs, highly similar to putative protein kinase C inhibitor[R. norvegicus] EST
CCTAGCCCCT 15 3 −3.0 0.047 7961 ESTs, weakly similar to transforming growth factor-beta (TGF-beta) masking protein large subunit [R. norvegicus] EST
CCTTTAATAA 15 3 −3.0 0.047 8405 ESTs, highly similar to CRP1_MOUSE cysteine-rich protein 1 (Cysteine-rich intestinal protein) (CRIP) [R. norvegicus] EST
TGGGTTGCTA 15 3 −3.0 0.047 None Novel tag Nov
CCCGTGTGCT 16 3 −3.2 0.034 3381 Ribosomal protein S9 (Rps9) Pro
ATTCTGATGA 23 4 −3.4 0.009 9448 ESTs EST
TGGTGCCTCT 23 4 −3.4 0.009 3061 Fatty acid coenzyme A ligase, long chain 5 (Facl5) Met, Lip
AACACTACGG 6 0 −3.6 0.046 4120 ESTs, weakly similar to S11349 nonhistone chromosomal protein HMG-17 EST
AAGAAAGGAG 6 0 −3.6 0.046 2910 Procollagen C-proteinase enhancer protein (Pcolce) CS/ECM
(continues)
Table 1D.
 
(continued). Differentially Regulated Transcripts in Dark-Reared Rat EOM
Table 1D.
 
(continued). Differentially Regulated Transcripts in Dark-Reared Rat EOM
Tag LR DR DR/LR P Unigene (RS) Gene Name Function
ACGCCCTTCA 6 0 −3.6 0.046 3292 ESTs, moderately similar to mitochondrial ribosomal protein S17 [M. musculus] EST
ACTACCGGGC 6 0 −3.6 0.046 37686 ESTs, moderately similar to S11276 alpha-adaptin c EST
AGGTCCTTGT 6 0 −3.6 0.046 None Novel tag Nov
CACGCCTTTC 6 0 −3.6 0.046 9215 Acetoacetyl-CoA synthetase (Hba1) Met, Lip
CACGCCTTTC 6 0 −3.6 0.046 11229 Hemoglobin, alpha 1 (Hba1) Oth
CATTGCGTGG 6 0 −3.6 0.046 2880 ESTs EST
CCCTGGTCAC 6 0 −3.6 0.046 None Novel tag Nov
CGCGGAGGCC 6 0 −3.6 0.046 11207 Thrombospondin 4 (Thbs4) CS/ECM
CGTGGATCCC 6 0 −3.6 0.046 12256 ESTs, moderately similar to CDNC_MOUSECYCLIN-DEPENDENT KINASE INHIBITOR 1C(CYCLIN-DEPENDENT KINASE INHIBITOR P57)(P57KIP2) [M. musculus] EST
CTTCAGCTAT 6 0 −3.6 0.046 22479 ESTs EST
GAAAGAAACT 6 0 −3.6 0.046 31991 Secreted acidic cystein-rich glycoprotein (osteonectin) C/D
GAACAATGGA 6 0 −3.6 0.046 8706 pR-ET2 encoded oncodevelopmental protein Imm
GACCAACAGA 6 0 −3.6 0.046 2953 Collagen, type 1, alpha 1 (Colla1) CS/ECM
GATATCAACT 6 0 −3.6 0.046 None Novel tag Nov
GATTCCCCCC 6 0 −3.6 0.046 16597 ESTs EST
GATTCTTCAG 6 0 −3.6 0.046 7262 Defender against cell death 1 C/D
GCACCGGGAA 6 0 −3.6 0.046 None Novel tag Nov
GCATATTTGA 6 0 −3.6 0.046 2026 ESTs, moderately similar to cytochrome c oxidase subunit VIIb; 1100001F07Rik [M. musculus] EST
GCTTTGGCTT 6 0 −3.6 0.046 31976 Branched chain keto acid dehydrogenase kinase (Bekdk) Met, Lip
GTTTCCCCTC 6 0 −3.6 0.046 None Novel tag Nov
TAAATTGTAG 6 0 −3.6 0.046 None Novel tag Nov
TCCCCTACAT 6 0 −3.6 0.046 None Novel tag Nov
TCCTCAGCAC 6 0 −3.6 0.046 6120 ESTs, highly similar to C54819 actin-capping protein beta chain, splice form 2 EST
TGATTCGGTT 6 0 −3.6 0.046 40162 ESTs EST
TGGACTGCTG 6 0 −3.6 0.046 11301 Mannosidase, alpha, class 2C, member (Man2c1) Oth
TGGCCAGGGC 6 0 −3.6 0.046 None Novel tag Nov
TGGGCCCCTG 6 0 −3.6 0.046 None Novel tag Nov
TTCAACCTCA 6 0 −3.6 0.046 16833 ESTs, weakly similar to ROD_RAT; heterogeneous nuclear ribonucleoprotein D0 (hnRNP D0; AU-rich element RNA-binding protein 1) [R. norvegicus] EST
TTTGGGAAAA 6 0 −3.6 0.046 52763 Ankyrin 3 (G) Cyto
TTTTTACTGA 6 0 −3.6 0.046 8450 ESTs, highly similar to integral membrane protein 3[M. musculus] EST
AAATAAAGAT 25 4 −3.7 0.005 4958 Sodium channel, voltage-gated, type 1, beta polypeptide (Scn1b) Rec
65438 ESTs
AAGACAGCTG 19 3 −3.8 0.013 39743 RT1 class Ib gene (RT1-R) Imm
37183 ESTs
83611 MHC class I RT1.O type 149 processed pseudogene
ACAGTGGGGA 13 2 −3.8 0.037 22995 ESTs, highly similar to pleckstrin 2 [M. musculus] EST
GTGTTCTATA 32 5 −3.8 0.001 None Novel tag Nov
CTTTATTCCA 33 5 −3.9 0.001 2953 Collagen, type 1, alpha 1 (Collal) CS/ECM
TCTTCTCACA 20 3 −3.9 0.009 6172 Ribosomal protein L39 (Rpl39) Pro
AAATGCTTGG 7 0 −4.1 0.029 74273 ESTs, weakly similar to S11661 talin EST
AAGTCCTTTT 7 0 −4.1 0.029 6211 Glucocorticoid-induced leucine zipper (Gilz) Trans
35608 ESTs
AATGGGAGGC 7 0 −4.1 0.029 None Novel tag Nov
ACCCCCAGTC 14 2 −4.1 0.026 81140 Thyroid hormone responsive protein (spot14) (Thrsp) Met, Lip
AGATGTATTT 7 0 −4.1 0.029 4178 ESTs, highly similar to RIKEN cDNA 1010001C05[M. musculus] EST
AGGCTGGTGA 7 0 −4.1 0.029 6016 Proteasome (prosome, macropain) subunit, beta type 1 (Psmb1) Imm, Pro
25100 ESTs
ATAACAACAT 7 0 −4.1 0.029 81261 EST EST
ATACACATAA 35 5 −4.1 4.3E-04 None Novel tag Nov
ATGAAGCCAG 14 2 −4.1 0.026 54594 Voltage-dependent anion channel 1 (Vdac1) Rec
ATGTAGCCAG 7 0 −4.1 0.029 20160 tRNA selenocysteine associated protein Pro
CAAACAATCA 7 0 −4.1 0.029 None Novel tag Nov
CACGGCCTCT 7 0 −4.1 0.029 None Novel tag Nov
CATTCGGAGA 7 0 −4.1 0.029 None Novel tag Nov
CCCAGCACTT 7 0 −4.1 0.029 22230 ESTs EST
GATCAAGTCA 7 0 −4.1 0.029 None Novel tag Nov
(continues)
Table 1E.
 
(continued). Differentially Regulated Transcripts in Dark-Reared Rat EOM
Table 1E.
 
(continued). Differentially Regulated Transcripts in Dark-Reared Rat EOM
Tag LR DR DR/LR P Unigene (RS) Gene Name Function
GCAATTATTG 7 0 −4.1 0.029 9197 ESTs EST
GCCGCAAAGG 7 0 −4.1 0.029 None Novel tag Nov
GGCAGAAACT 7 0 −4.1 0.029 None Novel tag Nov
GGGATGGACG 7 0 −4.1 0.029 30176 Complement component 4 Imm
TAGGCCACCC 7 0 −4.1 0.029 None Novel tag Nov
TAGGTGTGGG 7 0 −4.1 0.029 871 Calponin 3, acidic (Cnn3) Cyto, Mus
28172 ESTs
TCTATTCTCA 14 2 −4.1 0.026 None Novel tag Nov
GCTTCTCAGT 23 3 −4.5 0.003 11004 Phosphofructokinase, muscle (Pfkm) Met
AATCGAAGGC 8 0 −4.7 0.018 None Novel tag Nov
ATACCCATAA 8 0 −4.7 0.018 None Novel tag Nov
ATTTATTACA 8 0 −4.7 0.018 None Novel tag Nov
CCCTGAGTCC 24 3 −4.7 0.002 69 Ribosomal protein L14 Pro
CGCAAGGCCC 8 0 −4.7 0.018 49290 ESTs, highly similar to HTGN29 protein [H. sapiens] EST
GACACCTTGA 8 0 −4.7 0.018 35336 ESTs, weakly similar to hypothetical protein FLJ20559[H. sapiens] EST
GATCCCCCCA 8 0 −4.7 0.018 None Novel tag Nov
GCACTAGCTG 8 0 −4.7 0.018 37311 Progesterone receptor membrane component 1 (Pgrmc1) Rec
GCGCCCTGAG 8 0 −4.7 0.018 None Novel tag Nov
ACTCGGATGC 33 4 −4.9 2.8E-04 18013 ESTs, moderately similar to RIKEN cDNA 1810011O01[R. norvegicus] EST
AGCACAGTTA 33 4 −4.9 2.8E-04 13092 ESTs, weakly similar to RET1_RAT retinol-binding protein I; cellular (Cellular retinol-binding protein; CRBP)[R. norvegicus] EST
AGGTCCACCA 9 0 −5.3 0.011 None Novel tag Nov
ATACTGCACT 18 2 −5.3 0.006 None Novel tag Nov
ATACTGCCAC 9 0 −5.3 0.011 None Novel tag Nov
GCCTCCAAGA 9 0 −5.3 0.011 1002 Plasminogen activator, tissue (Plat) CS/ECM
GCGGTGGCAG 9 0 −5.3 0.011 38807 ESTs EST
GGTGAGGTTT 9 0 −5.3 0.011 3870 ESTs, moderately similar to hypothetical protein MNCb-0169 [M. musculus] EST
TGAGGTCTTG 9 0 −5.3 0.011 8476 ESTs EST
CAGCTCTGGG 10 1 −5.9 0.036 15228 ESTs, highly similar to toll-associated serine protease[M. musculus] EST
CTCCGAGAGG 10 1 −5.9 0.036 4287 ESTs, weakly similar to A43932 mucin 2 precursor, intestinal EST
CTCTCTAAAC 10 1 −5.9 0.036 947 ESTs, weakly similar to B26423 serin proteinase inhibitor 2.2 EST
GATGTGACCA 10 1 −5.9 0.036 125 ESTs, highly similar to eukaryotic translation initiation factor 3, subunit 2 (beta, 36kD); TGF-beta receptor binding protein; DNA segment, Chr 4, ERATO Doi 632, expressed [M. musculus] EST
TAGGTACAGC 10 0 −5.9 0.007 None Novel tag Nov
TCTGAATCTT 10 0 −5.9 0.007 None Novel tag Nov
TTATTTGGTG 10 1 −5.9 0.036 34356 ThyM.cell surface antigen Imm, CS/ECM
AAAACACATA 11 1 −6.5 0.024 None Novel tag Nov
GCCTCTGCTG 11 1 −6.5 0.024 3777 ESTs, moderately similar to RIKEN cDNA 2310040G17; expressed sequence AI425883 [M. musculus] EST
AATGCCCCCC 71 6 −7.0 2.7E-09 None Novel tag Nov
AAACTGACAC 12 1 −7.1 0.016 None Novel tag Nov
CTGAAAAAAA 12 1 −7.1 0.016 81140 Thyroid hormone responsive protein (spot14) (Thrsp) Met, Lip
6510 ESTs, highly similar to mannosidase, beta A, lysosomal-like[H. sapiens]
GCTCCCAGGG 12 1 −7.1 0.016 23659 ESTs EST
GGGTCAACTG 12 0 −7.1 0.003 4083 S-100 related protein, clone 42C (S100a10) Sig, C/D
TTTGGGAGAA 12 0 −7.1 0.003 None Novel tag Nov
CTGGAGCATC 13 1 −7.7 0.011 68036 ESTs EST
ATAACCCATA 14 1 −8.3 0.007 None Novel tag Nov
ATACCACATA 14 1 −8.3 0.007 None Novel tag Nov
ATATTGACAC 15 1 −8.9 0.005 None Novel tag Nov
ATAACACAAT 16 0 −9.5 4.4E-04 None Novel tag Nov
CCCTGAGCGG 17 1 −10.1 0.002 2514 Transferrin (Tf) Rec
ATACTTGACA 61 3 −12.0 8.9E-10 25364 ESTs EST
Table 2.
 
Differentially Regulated Transcripts in Monocularly Deprived Monkey Lateral Rectus
Table 2.
 
Differentially Regulated Transcripts in Monocularly Deprived Monkey Lateral Rectus
GenBank Acc. No. Gene Name Symbol Change (×) Function
NM_018563 Hypothetical protein PR00758 PRO0758 48.5 Unknown
AF094508 Dentin sialophosphoprotein DSPP 4.1 Extracellular matrix
NM_015978 Putative protein-tyrosine kinase LOC51086 2.7 Unknown
NM_025012 Hypothetical protein FLJ13769; FLJ13769 2.4 Unknown
BG252666 ATPase, Class I, type 8B; member 1 ATP8B1 2.3 Aminophospholipid transport
NM_000393 Collagen, type V, alpha 2 COL5A2 −1.8 Extracellular matrix
AU144167 Collagen, type III, alpha 1 (Ehlers-Danlos syndrome type IV; autosomal dominant) COL3A1 −1.8 Extracellular matrix
NM_002048 Growth arrest-specific 1 GAS1 −1.9 Cell proliferation and growth
NM_000089 Collagen, type I, alpha 2 COL1A2 −1.9 Extracellular matrix
M97935 Signal transducer and activator of transcription 1, 91kDa STAT1 −2.0 Signal transduction; cell proliferation and growth
NM_000088 Collagen, type I, alpha 1 COL1A1 −2.0 Extracellular matrix
AF138300 Decorin DCN −2.1 Extracellular matrix
AF130082 Hypothetical protein PRO3121 PRO3121 −2.1 Unknown
AV753392 Heterogeneous nuclear ribonucleoprotein HNRPH1 −2.2 RNA processing
AF138302 Decorin DCN −2.3 Extracellular matrix
BF514079 cDNA FLJ38575 fis, clone HCHON2007046, mRNA sequence −2.4 Unknown
NM_002065 Glutamate-ammonia ligase (glutamine synthase) GLUL −2.7 Amino acid metabolism and NO biosynthesis
A1813758 Collagen, type III, alpha 1 (Ehlers-Danlos syndrome type IV, autosomal dominant) COL3A1 −2.7 Extracellular matrix
NM_002612 Pyruvate dehydrogenase kinase, isoenzyme 4 PDK4 −4.7 Glycolysis
NM_022831 Hypothetical protein FLJ12806 FLJ12806 −7.9 Unknown
Table 3.
 
Differentially Regulated Transcripts in Monocularly Deprived Monkey Medial Rectus
Table 3.
 
Differentially Regulated Transcripts in Monocularly Deprived Monkey Medial Rectus
GenBank Acc. No. Gene Name Symbol Change (×) Function
L12711 Transketolase (Wernicke-Korsakoff syndrome) TKT 7.1 Pentose phosphate pathway
U63131 CDC37 cell division cycle 37 homologue S. cerevisiae) CDC37 3.6 Cell cycle regulation; cell proliferation and growth
J03068 N-acylaminoacyl-peptide hydrolase APEH 2.8 Amino acid metabolism
NM_000703 ATPase, Na+/K+ transporting, alpha 3 polypeptide ATP1A3 2.8 Cation transport
NM_001540 Heat shock 27kD protein 1 HSPB1 2.7 Protein modification; stress response
NM_002541 Oxoglutarate (alpha-ketoglutarate) dehydrogenase (lipoamide) OGDH 2.3 Energy metabolism
NM_002869 RAB6A, member RAS oncogene family RAB6A 2.3 GTPase; membrane transport
AF172268 KIAA0551 protein KIAA0551 2.1 Unknown
NM_002397 MADS box transcription enhancer factor 2, polypeptide C (myocyte enhancer factor 2C) MEF2C 1.9 Myogenesis
NM_005729 Peptidylprolyl isomerase F (cyclophilin F) PPIF 1.9 Protein modification
NM_005952 Metallothionein IX MTIX −1.8 Heavy metal binding
BC001971 Cyclin-dependent kinase inhibitor 1B (p27, Kip1) CDKN1B −1.8 Cell cycle regulation; cell proliferation and growth
NM_001186 BTB and CNC homology 1, basic leucine zipper transcription factor 1 BACH1 −1.8 Transcription
AL161952 Glutamate-ammonia ligase (glutamine synthase) GLUL −1.9 Amino acid metabolism
NM_001855 Collagen, type XV, alpha 1 COL15A1 −1.9 Extracellular matrix
M83772 Flavin-containing monooxygenase 3 FMO3 −1.9 Microsome
BF791738 Hypothetical protein PRO2751 PRO2751 −2.0 Unknown
AF153330 Solute carrier family 19 (thiamin transporter), member 2 SLC19A2 −2.1 Transporter
NM_000161 GTP cyclohydrolase 1 (dopa-responsive dystonia) GCH1 −2.1 Amino acid metabolism; biosynthesis of NO
BF514079 cDNA FLJ38575 fis, clone HCHON2007046, mRNA sequence −2.4 Unknown
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