February 2004
Volume 45, Issue 2
Free
Retina  |   February 2004
Electroretinography as a Screening Method for Mutations Causing Retinal Dysfunction in Mice
Author Affiliations
  • Claudia Dalke
    From the GSF-National Research Center for Environment and Health, Institutes of Developmental Genetics,
  • Jana Löster
    From the GSF-National Research Center for Environment and Health, Institutes of Developmental Genetics,
  • Helmut Fuchs
    Experimental Genetics, and
  • Valerie Gailus-Durner
    Experimental Genetics, and
  • Dian Soewarto
    Experimental Genetics, and
  • Jack Favor
    Human Genetics and Clinical Cooperation Group Ophthalmogenetics, Neuherberg, Germany; and the
  • Angelika Neuhäuser-Klaus
    Human Genetics and Clinical Cooperation Group Ophthalmogenetics, Neuherberg, Germany; and the
  • Walter Pretsch
    Human Genetics and Clinical Cooperation Group Ophthalmogenetics, Neuherberg, Germany; and the
  • Florian Gekeler
    University Eye Hospital, Tübingen, Germany.
  • Kei Shinoda
    University Eye Hospital, Tübingen, Germany.
  • Eberhart Zrenner
    University Eye Hospital, Tübingen, Germany.
  • Thomas Meitinger
    Human Genetics and Clinical Cooperation Group Ophthalmogenetics, Neuherberg, Germany; and the
  • Martin Hrabé de Angelis
    Experimental Genetics, and
  • Jochen Graw
    From the GSF-National Research Center for Environment and Health, Institutes of Developmental Genetics,
Investigative Ophthalmology & Visual Science February 2004, Vol.45, 601-609. doi:https://doi.org/10.1167/iovs.03-0561
  • Views
  • PDF
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Claudia Dalke, Jana Löster, Helmut Fuchs, Valerie Gailus-Durner, Dian Soewarto, Jack Favor, Angelika Neuhäuser-Klaus, Walter Pretsch, Florian Gekeler, Kei Shinoda, Eberhart Zrenner, Thomas Meitinger, Martin Hrabé de Angelis, Jochen Graw; Electroretinography as a Screening Method for Mutations Causing Retinal Dysfunction in Mice. Invest. Ophthalmol. Vis. Sci. 2004;45(2):601-609. doi: https://doi.org/10.1167/iovs.03-0561.

      Download citation file:


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

      ×
  • Supplements
Abstract

purpose. To detect mice with hereditary retinal impairment, a high-throughput electroretinography (ERG) screening system was established.

method. Mice from eight different strains without known retinal disorders (102, 129/SvJ, AKR, C57BL/6J, C57BL/6JIco, CBA/CaJ, and DBA/2NCrlBR) and one control strain with retinal degeneration (C3HeB/FeJ) were fixed on a specially constructed sled, ERG electrodes were placed on the cornea, and mice were moved into a Ganzfeld stimulator. From a luminance range of 0.0125 to 500 cd-s/m2 in a pretest series two levels (5 and 125 cd-s/m2) were chosen to shorten examination times. The root mean square (RMS) of the ERG-recording was analyzed to detect animals with abnormal retinal function. ERG responses of the left and right eyes were compared in amplitudes and implicit times of the a- and b-waves. Statistical analysis of the latter parameters was performed in all wild-type animals. Histology was performed on selected mice.

results. ERG recordings of individual animals for the left and right eye revealed good agreement in amplitudes and implicit times of the a- and b-waves (P < 0.05). Comparison of these parameters among the wild-type strains showed several differences. Evaluation of the RMS revealed, in addition to the C3HeB/FeJ mice, a subgroup of mice within the 129/SvJ strain with abnormal retinal function. Molecular analysis of these mice demonstrated the presence of the same retroviral insertion in the Pde6b gene, which is causative of the Pde6b rd1 allele carried in C3HeB/FeJ mice. Histologic analysis demonstrated good correlation between retinal electrophysiology and morphology.

conclusions. The present results demonstrate the feasibility of ERG for screening a large number of mice to detect animals with functional retinal impairment.

Human retinal disorders cover a broad variety of clinical symptoms and many different genes are involved in the corresponding pathologic conditions. The two most important groups are retinitis pigmentosa (RP) and age-related-macular-degeneration (ARMD). In Germany, approximately 10% and 15% of legal blindness is caused by these two groups, respectively. 1 Worldwide, the prevalence of RP is approximately 1:4000. The reasons for the progressive loss of photoreceptors (PRs) are genetic abnormalities at more than 100 gene loci, affecting various ocular tissues (for a recent review, see Ref. 2 ; and corresponding web sites at http://eyegene.meei.harvard.edu or http://www.sph.uth.tmc.edu/RetNet). A few examples for these human disorders will be described. 
ARMD is the leading cause of blindness in the elderly in developed countries. A complex series of events ultimately leads to degeneration of PRs. Various etiologies are currently proposed for this disease, with genetic factors considered as major components. ARMD is considered a genetically complex disease, but in contrast to RP, only candidate genes can be discussed. 3 In contrast, there are some congenital diseases with a clear genetic background. One of them is Stargardt’s disease, which is transmitted mainly as an autosomal-recessive trait with a prevalence of 1:10,000. Mutations in a few genes have been shown to be causative of particular forms. 4 5 6  
Moreover, a combination of the clinical features of RP with deafness is referred to as Usher syndrome (USH); it is also transmitted as an autosomal-recessive trait with a frequency of 1:16.000 (for a recent review, see Ref. 7 ). In Usher syndrome, several subtypes have been reported, and causative mutations have been identified in a variety of genes (examples are given in Refs. 8 9 10 11 12 13 14 ). 
Leber’s congenital amaurosis (LCA) affects children very early in life with a frequency of 1:40,000 in an autosomal-recessive or sometimes autosomal-dominant manner. It accounts for 10% to 18% of cases of congenital blindness. Several genes have been identified as involved in the pathogenesis of LCA, but mutations in RPE65 are responsible for 10% to 15% of all cases, and mutations in CRX are responsible for the dominant form of LCA (for a recent review, see Ref. 15 ). Later, teenagers and young adults are affected with a similar frequency (1:40,000) by cone–rod dystrophies (CORDs). Clinically, the CORDs are heterogeneous, which is reflected also by their genetic heterogeneity. CORD can be inherited in an autosomal-recessive, autosomal-dominant, or X-linked manner. Causative mutations have been identified in several genes. 16 17 18 19 20 21 22 23 Mutations in some genes are attributed to different disorders—for example, mutations in ABC4A, which lead to CORD3 17 or STGD1. 4  
Even if this short survey suggests that some retinal disorders can be attributed to mutations in particular genes, many of these retinal diseases remain to be characterized functionally, to understand the various mechanisms underlying the clinical features of retinal degeneration and develop strategies for therapeutic intervention. Therefore, mouse models reflecting the broad variety of human genetic disorders would be desirable to characterize the physiological mechanisms in these phenotypic deviants. Most of the mouse models available to date were designed as transgenic or knockout mice. Several targeted mutations have been constructed that affect different ocular structures such as the retinal pigment epithelium (e.g., Rpe65, 24 Rbp4, 25 and Mertk 26 ) and transport and membrane channels (Cng3). 27 However, most of the targeted mutations affect the photoreceptors (representative models affect Abcr, 28 arrestin, 29 Crx, 30 Rep1, 23 Rho, 31 Rhok, 32 Rom1, 33 Rpgr, 34 or Tulp1 35 ). However, these null mutations do not reflect the clinical situation in all cases, because mutations in genes that affect the general metabolism (such as the RBP4 gene) also affect retinal function. 36  
One reason is that many retinal disorders are transmitted as complex traits. Experimentally, the transmission of these disorders can be investigated by the use of double transgenics or double knockouts. One example (Rpe65 −/− /Cnga3 −/− ) has been published recently. 37 However, spontaneous or randomly induced mouse mutations may be closer to the human situation. Only a few such mouse mutations have been described, such as the rd1 mutation as a retroviral integration in the Pde6b gene, 38 the rds/rd2 mutation affecting the Prph2 gene, 39 or the or1 allele in the Chx10 gene. 40 A list of an additional 16 spontaneous mouse mutants affecting retinal function was published recently, but only a few have been characterized at a molecular level and assigned to known genes such as Pde6b, Prph2, or Mitf. 41  
Therefore, we established a systematic screen for mutations in mice using a functional assay. Herein, we report the analysis of the baselines in various wild-type strains of mice. We detected the Pde6b rd1 mutant allele segregating in strain 129/SvJ, which was considered previously to be wild-type with respect to retinal degeneration. This finding demonstrates the feasibility of the current method, which allows in the German Mouse Clinic (GMC; http://www.gsf.de/ieg/gmc/index.html) a high-throughput screening of mice derived from parents treated by the mutagenic agent ethylnitrosourea (ENU). 
Methods
Animals
Eight different mouse strains, which were considered up to now in many laboratories to be wild-type for retinal degeneration, were included in the study: 102 (n = 8), 129/SvJ (n = 10), AKR (n = 7), C57BL/6J (n = 10), C57BL/6JIco (n = 10), CBA/CaJ (n = 11), DBA/2NCrlBR (n = 6), and JF1 (n = 8). As an established control for hereditary retinal degeneration 42 we used mice from the strain C3HeB/FeJ (n = 10). If not otherwise stated, mice were 6 weeks old at the time of analysis. DBA/2NCrlBR mice were bought from Charles River (Kissleg, Germany). All other strains were bred in the GSF Research Center. Experiments and housing of the animals were performed according to the German Law on the Protection of Animals (Regulation 209-2531-55/01 by the Government of Upper Bavaria) and the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. 
Electroretinography
Mice were dark adapted for at least 12 hours and anesthetized with 137 mg ketamine and 6.6 mg xylazine per kilogram body weight. After pupil dilation (1 drop atropine 1%), individual mice were fixed on a sled with Velcro straps. Gold wire loops as active electrodes were placed on both corneas. Care was taken not to obstruct the pupillary opening. The ground electrode was a subcutaneous needle in the tail. A reference electrode was placed subcutaneously between the eyes. The mice were introduced into a handheld Ganzfeld LED stimulator (Espion ColorBurst; Diagnosys LLC, Littleton, MA) on a rail to guide the sled (High-Throughput Mouse ERG setup, Steinbeis-Transfer Centre for Biomedical Optics and Function Testing, Tübingen, Germany). 43 The setup is depicted in Figure 1 . Electrode impedance was checked before and after each measurement in both eyes separately in all animals using the machine’s built-in algorithm and was found to be less than 10 kΩ at 50 Hz (manufacturer’s recommendation). To minimize temperature influences on the ERG, body temperature was kept at 36.5°C with a warming plate. Light pulses (10 ms) were delivered at a frequency of 0.48 Hz in 10 steps at 0.0125, 0.025, 0.125, 0.5, 12.5, 5, 12.5, 50, 125 and 500 cd-s/m2. This rather high frequency was chosen to allow rapid data acquisition for screening purposes. Time between consecutive steps was approximately 1 minute. Responses were recorded simultaneously from both eyes (Espion Console; Diagnosys LLC, Littleton, MA) and stored for off-line analysis after averaging 10 to 40 individual measurements at each step. A bandpass filter was set to range from 0.15 to 1000 Hz. 
Statistics
A specially written computer program (MatLab; The MathWorks, Natick, MA) was used to search for minima and maxima to determine a- and b-waves automatically (a-wave amplitude was defined as the minimum between 0 and 50 ms; b-wave amplitude was defined as the difference between the a-wave and the maximum between 30 and 200 ms). The Naka-Rushton fits for the amplitude of the b-wave 44 were iteratively performed. Data retrieved by the computer program were checked individually by an experienced electrophysiologist to ensure that the proper peaks have been detected. Special attention had to be paid to the correct determination of the b-wave in step 2 to exclude bias from overlying oscillatory potentials (OPs), although in most cases, none of the large OPs caused interference. The following comparisons were performed: (1) root mean square (RMS) 45 of ERG recordings (between 0 and 200 ms) of individual mice to detect animals with functional impairment; (2) amplitude and implicit time of a- and b-waves in step 1 and 2 in all mice, to assess the agreement between left and right eyes; and (3) amplitude and implicit time of a- and b-waves in all mice without known retinal impairment, to assess differences between groups considered normal. Because measurements were made across eight different strains (which were initially thought to be wild-type with respect to retinal degeneration) and one blind control strain carrying the Pde6b rd1 mutation with the possibility of multiple pair-wise comparisons, the significance of the differences between (1) and (3) were evaluated by ANOVA followed by the Scheffé post hoc F test. In (2) a Bland-Altman analysis 46 was performed to reveal any relationship between the differences in the right and left eyes and their averages. 
Morphologic Analysis
For the morphologic analysis and documentation of retinal degeneration, eyes were fixed for 24 hours in Davidson solution, dehydrated, and embedded in paraffin or plastic medium (JB4-Plus; Polysciences, Inc., Eppelheim, Germany) according to the manufacturer’s procedure. Sectioning was performed with an ultramicrotome (Ultratom OMU3; Reichert, Walldorf, Germany). Serial transverse 2-μm sections were cut with a dry glass knife and collected in water drops on glass slides. After drying, the sections were stained with methylene blue and basic fuchsin and evaluated with a light microscope (Axioplan; Carl Zeiss Meditec, Göttingen, Germany). Images were acquired by means of a scanning camera (Axiocam; Carl Zeiss Meditec) equipped with a screen-capture program (KS100; Carl Zeiss Vision, Hallbergmoos, Germany) and imported into an image-processing program (Illustrator, ver. 9.0, or Photoshop, ver. 6.0; Adobe, Unterschleissheim, Germany). 
Isolation of DNA and PCR Conditions
Genomic DNA was prepared from tail tips of the mice according to standard procedures. To detect the Xmv-28 insertion in the Pde6b gene leading to retinal degeneration (rd1), we amplified the corresponding region using the primers 10 and JS610 essentially as described previously 47 with 35 cycles (MJ Research PTC-225 machine; Biozym Diagnostik GmbH, Hess, Oldendorf, Germany) using 67°C annealing temperature. PCR products were separated in a 1% agarose gel. 
General
Chemicals were purchased from Merck (Darmstadt, Germany) or Sigma-Aldrich (Deisenhofen, Germany). The enzymes and ingredients for PCR were from Invitrogen or Roth (both Karlsruhe, Germany) or from MBI Fermentas (St. Leon-Rot, Germany). 
Results
From a preliminary series with 10 C57BL/6J mice at 10 different luminance levels two levels at 5 and 125 cd-s/m2 were chosen that produced reliable responses and easily detectable peaks and represented two quite different illumination ranges, and because a luminance of 5 cd-s/m2 (step 1) evoked a well discernible b-wave amplitude mainly stemming from the rod system, whereas 125 cd-s/m2 (step 2) evoked a saturated b-wave response with an a-wave, mediated presumably by a mixed rod and cone input (Fig. 2A) . The restriction to a two-step screening system shortened the examination time and provided stable measurement conditions. The setup used in this study allowed two people to screen 20 to 25 mice every 4 hours. 
One subset of five animals of the 129/SvJ strain showed no recognizable a- or b-waves and C3HeB/FeJ mice showed greatly diminished ERG responses (step 1: one animal with recognizable, but diminished a- and b-waves; step 2: five animals with recognizable, but diminished a- and b-waves). These two groups were found to be significantly different in terms of the RMS in all other groups in step 1, including the remaining normal mice of strain 129/SvJ. In step 2, all groups except JF1 were significantly different from the subset of 129/SvJ and C3HeB/FeJ mice (Fig. 3) . Retinal impairment in these two groups (129/SvJ were termed 129/SvJblind and C3HeB/FeJ) were confirmed by morphologic examination (described later) and excluded from further analysis of ERG components. In addition, we found statistically significant differences of the RMS between the following normal strains: JF1 versus 102, JF1 versus AKR, JF1 versus CBA/CaJ, CBA/CaJ versus C57BL/6JIco, and CBA/CaJ versus DBA/2NCrlBR (Fig. 3)
Subsequently, Bland-Altman analysis of the amplitudes and implicit times of a- and b-waves of steps 1 and 2 in the right and left eyes (Table 1) did not reveal any systematic or proportional error or any dependence on the magnitude of the values. According to the suggestion of Bland and Altman 46 the two measurements can be used interchangeably or, in our case, the left and right eyes can be averaged for further detailed statistical evaluation (Fig. 4) . Within the eight strains of normal mice, a- and b-waves were compared in steps 1 and 2 for amplitude and implicit time. The Scheffé post hoc F test revealed three statistically significant differences in amplitude and six differences in implicit time (Table 2)
Histologic evaluation of all mice with a typical wild-type ERG response showed well-ordered retinal layers. C3HeB/FeJ mice, which are homozygous Pde6b rd1 , showed no ERG response and had degenerated photoreceptor layers. The overall histologic appearance of the retinas of the 129/SvJblind mice was similar to that of C3HeB/FeJ (Fig. 5)
Because the retinal degeneration in the C3HeB/FeJ mouse strain had been demonstrated to be caused by a retroviral insertion into the Pde6b gene, 38 we tested for the presence of the Pde6b rd1 allele in all strains used during this study. The presence of the Pde6b rd1 allele in our C3HeB/FeJ mice was confirmed. All 129/SvJblind mice were found to be homozygous for the Pde6b rd1 allele. Among those 129/SvJ mice with a normal ERG response, we found some to be carrying the Pde6b rd1 allele, presumably heterozygotes (data not shown). All other strains tested were negative for this insertion (Fig. 6)
To identify the most feasible age of screening, we checked in our C57BL/6J colony six age points by ERG (at 125 cd-s/m2). The ERG response increased and reached its maximum at 8.5 weeks of age (Fig. 7) , which is in good agreement with Li et al., 48 who have shown that saturation is reached at 8 weeks of age. At this age, the mice had a fully developed retina, and the animals were big enough to be easily fixed on the sled for ERG measurement. However, we chose 6 weeks of age in accordance with previous studies. 26 49 50 Even if it is a compromise to minimize animal handling and housing costs by screening animals as early as possible, we were able to detect all animals with retinal degeneration correctly when examined at 6 weeks of age. 
Discussion
We successfully developed a high-throughput protocol on the basis of ERG as a quick, robust, and reproducible in vivo screening method for inherited functional retinal impairment in mice. The data obtained demonstrate that there is no major left–right difference in the ERG responses. However, in each strain, individual mice showed variation, making further statistical evaluation necessary in most cases. Two groups, one of them being C3HeB/FeJ and one of them consisting of a subset of five animals of the 129/SvJ strain, showed either no discernible a- or b-wave (10 animals) or greatly diminished amplitudes. The animals with no discernible a- or b-wave are easily detected during the screening process and showed significantly lower RMS values in the ERG recordings. 
For screening purposes the b-wave amplitude seems to be the most stable and informative end point, because of its magnitude and high sensitivity due to the input of the originating cells. We suggest that outliers be defined as those animals with ERG responses outside the 95% confidence interval (which was calculated from the normal subjects in the present study). Animals with ERG responses less than the lower limit should undergo further ERG evaluation before undergoing the histologic and genetic tests. The lower limits calculate to 76 μV (step 1) or 97 μV (step 2) for amplitude. All animals with morphologically and genetically certain retinal degeneration (as proven later in the process by histology and genetical analysis) were correctly classified based on our defined criterion with respect to amplitude of the b-wave. This criterion is easily checked by the technician during a fast screening process, to detect animals with a suspected retinal disease to take appropriate action in the later evaluation process. 
The method suggested above was validated by the examination of C3HeB/FeJ mice, which are known to be homozygous for the mutant allele Pde6b rd1 . 38 They showed ERG responses significantly reduced in comparison to all wild-type strains. Moreover, the screening method is also robust for the detection of individual mice with impaired retinal function as demonstrated for a subset of mice from the 129/SvJ strain. In these mice, the ERG response showed no discernible a- or b-waves. They were found to be statistically different in their RMS value. As a first molecular characterization, we checked all our strains investigated for the presence or absence of the retroviral insertion causative of the Pde6b rd1 allele. 38 Those 129/SvJ mice with no discernible ERG response were shown to be homozygous Pde6b rd1 . Among the 129/SvJ with normal ERG, some were homozygous wild type and others were heterozygous Pde6b rd1 , indicating that the Pde6b rd1 allele segregates in our 129/SvJ stock and is expressed recessively. Moreover, these results validate the method applied to identify outliers such as 129/SvJblind
The strain 129 is widely used for the generation of targeted mutations (knockouts). A large degree of genetic diversity among the 129 substrains was recently identified. 51 52 In particular, the strain 129/SvJ was genetically contaminated in approximately 1978 by an unknown strain and differs from other 129 substrains at approximately 25% of simple sequence length polymorphism (SSLP) genetic markers. Therefore, it is most likely that it affects also the presence of the Pde6b rd1 allele in other 129/SvJ colonies. 
In conclusion, the newly established system reported herein is quick and sensitive and allows a high-throughput screening in mice. Therefore, we will apply this system to screen ENU-mutagenized mice to develop new mouse models of retinal degeneration. 
 
Figure 1.
 
Electroretinography on fixed, anesthetized mice. The handheld Ganzfeld stimulator is fixed at the bottom, and the mouse is moved on its sled into the position for examination with both eyes within the Ganzfeld bowl.
Figure 1.
 
Electroretinography on fixed, anesthetized mice. The handheld Ganzfeld stimulator is fixed at the bottom, and the mouse is moved on its sled into the position for examination with both eyes within the Ganzfeld bowl.
Figure 2.
 
Intensity series of corneal electroretinograms in one representative strain C57BL/6J mouse. (A) Traces show averages of 10 individual responses to a luminance of (1) 0.0125; (2) 0.025; (3) 0.125; (4) 0.5; (5) 1.25; (6) 5; (7) 12.5; (8) 50; (9) 125; and (10) 500 cd-s/m2. For screening purposes in all other groups, 5 and 125 cd-s/m2 were chosen as step 1 and step 2 (bold traces), respectively, to shorten examination times. (B) (♦) amplitudes of the b-waves. The line shows the Naka-Rushton fit in this mouse.
Figure 2.
 
Intensity series of corneal electroretinograms in one representative strain C57BL/6J mouse. (A) Traces show averages of 10 individual responses to a luminance of (1) 0.0125; (2) 0.025; (3) 0.125; (4) 0.5; (5) 1.25; (6) 5; (7) 12.5; (8) 50; (9) 125; and (10) 500 cd-s/m2. For screening purposes in all other groups, 5 and 125 cd-s/m2 were chosen as step 1 and step 2 (bold traces), respectively, to shorten examination times. (B) (♦) amplitudes of the b-waves. The line shows the Naka-Rushton fit in this mouse.
Figure 3.
 
RMS values in all mice in all groups. To detect mice with functional retinal impairment the RMS value of each group was compared with all other groups. The C3H and the 129/SvJblind strains showed statistically significant difference to all other normal groups in step 1. In step 2 these two groups were different from all other groups except for JF1. In addition, we found statistically significant differences of the RMS between the following normal strains in step 2: JF1 versus 102, JF1 versus AKR, JF1 versus CBA/CaJ, CBA/CaJ versus C57BL/6JIco, and CBA/CaJ versus DBA/2NCrlBR.
Figure 3.
 
RMS values in all mice in all groups. To detect mice with functional retinal impairment the RMS value of each group was compared with all other groups. The C3H and the 129/SvJblind strains showed statistically significant difference to all other normal groups in step 1. In step 2 these two groups were different from all other groups except for JF1. In addition, we found statistically significant differences of the RMS between the following normal strains in step 2: JF1 versus 102, JF1 versus AKR, JF1 versus CBA/CaJ, CBA/CaJ versus C57BL/6JIco, and CBA/CaJ versus DBA/2NCrlBR.
Table 1.
 
Bland-Altman Analysis of Amplitude and Implicit Time of Right and Left Eyes in Steps 1 and 2
Table 1.
 
Bland-Altman Analysis of Amplitude and Implicit Time of Right and Left Eyes in Steps 1 and 2
Amplitude (μV) Implicit Time (ms)
a-Wave b-Wave a-Wave b-Wave
Step 1 Step 2 Step 1 Step 2 Step 1 Step 2 Step 1 Step 2
Average of all eyes −11.2 −33.1 140.3 162.2 28.3 26.7 99.1 79.9
Mean of right-left eye 1.4 1.6 2.9 −8.3 −0.3 −0.2 −0.3 −0.4
SD of right-left eye 4.3 12.4 42.9 52.0 3.6 1.9 7.2 10.1
Percentage of eyes within 2 SD-range 95.1 95.2 93.8 96.9 92.7 95.2 92.3 93.8
Figure 4.
 
Comparisons of left and right eye recordings by linear regression analysis. (A) Amplitude of step 1 of a- and b-waves (r = 0.729 and 0.408, respectively, both P < 0.0001), (B) amplitude of step 2 of a- and b-wave (r = 0.686 and 0.245, P < 0.0001 and < 0.05, respectively), (C) implicit time of step 1 of a- and b-wave (r = 0.867 and 0.919, respectively, both P < 0.0001), (D) implicit time of step 2 of a- and b-wave (r = 0.954 and 0.942, respectively, both P < 0.0001).
Figure 4.
 
Comparisons of left and right eye recordings by linear regression analysis. (A) Amplitude of step 1 of a- and b-waves (r = 0.729 and 0.408, respectively, both P < 0.0001), (B) amplitude of step 2 of a- and b-wave (r = 0.686 and 0.245, P < 0.0001 and < 0.05, respectively), (C) implicit time of step 1 of a- and b-wave (r = 0.867 and 0.919, respectively, both P < 0.0001), (D) implicit time of step 2 of a- and b-wave (r = 0.954 and 0.942, respectively, both P < 0.0001).
Table 2.
 
ERG Parameters of Each Normal Group
Table 2.
 
ERG Parameters of Each Normal Group
Group a-Wave b-Wave
Step 1 Step 2 Step 1 Step 2
Amplitude [μV]
 102 −12.2 ± 3.3 −27.7 ± 12.6 137.6 ± 10.9 165.3 ± 10.7
 129/SvJ −12.6 ± 4.7 −22.5 ± 10.0 124.0 ± 35.9 159.1 ± 46.5
 AKR −11.1 ± 2.1 −38.5 ± 15.0 163.5 ± 21.0 177.8 ± 17.0
 C57BL/6J −10.5 ± 3.4 −41.6 ± 8.6 148.9 ± 36.1 179.2 ± 9.8
 C57BL/6Jlco −7.9 ± 4.5 −39.8 ± 17.5 148.3 ± 38.7 172.1 ± 46.1
 CBA/CaJ −12.9 ± 5.3 −20.7 ± 11.6 145.6 ± 27.2 167.6 ± 28.8
 DBA/2NCrlBR −10.9 ± 7.3 −32.4 ± 7.1 119.2 ± 14.7 132.3 ± 14.2
 JF1 −13.5 ± 7.2 −36.1 ± 7.5 120.6 ± 31.9 126.5 ± 15.7
Implicit time [ms]
 102 23.4 ± 5.6 26.4 ± 3.0 110.8 ± 11.3 92.1 ± 14.5
 129/SvJ 23.5 ± 7.5 26.4 ± 3.6 102.4 ± 8.4 80.0 ± 7.4
 AKR 25.7 ± 2.1 25.7 ± 1.7 81.6 ± 5.9 69.6 ± 8.0
 C57BL/6J 28.3 ± 9.2 25.9 ± 2.2 103.3 ± 17.8 72.4 ± 7.1
 C57BL/6Jlco 29.6 ± 5.9 28.6 ± 5.5 98.2 ± 13.2 75.2 ± 9.0
 CBA/CaJ 24.0 ± 3.5 22.1 ± 3.9 107.5 ± 12.9 91.8 ± 19.5
 DBA/2NCrlBR 30.5 ± 4.3 29.8 ± 2.0 92.8 ± 15.5 75.2 ± 10.1
 JF1 36.2 ± 4.0 29.6 ± 3.5 90.1 ± 10.6 61.4 ± 4.1
Figure 5.
 
The ERG response corresponded to retinal histology. The ERG response of one mouse is given together with the histology of its retina. The mouse strains used are C57BL/6J, C57BL/6JIco, C3HeB/FeJ, 129/SvJblind, 129/SvJ, CBA/CaJ, DBA/2NCrlBR, 102, and AKR. GCL, ganglion cell layer; INL, inner nuclear layer; IPL, inner plexiform layer; PE, pigmented epithelium; OFL, outer fiber layer; ONL, outer nuclear layer; OPL, outer plexiform layer.
Figure 5.
 
The ERG response corresponded to retinal histology. The ERG response of one mouse is given together with the histology of its retina. The mouse strains used are C57BL/6J, C57BL/6JIco, C3HeB/FeJ, 129/SvJblind, 129/SvJ, CBA/CaJ, DBA/2NCrlBR, 102, and AKR. GCL, ganglion cell layer; INL, inner nuclear layer; IPL, inner plexiform layer; PE, pigmented epithelium; OFL, outer fiber layer; ONL, outer nuclear layer; OPL, outer plexiform layer.
Figure 6.
 
Molecular analysis for the presence of the Pde6b rd1 allele. Genomic DNA of all mouse strains tested in this study was checked by PCR for the presence or absence of the Pde6b rd1 allele. C3HeB/FeJ mice as well as in 129/SvJblind mice with lowered ERG response were shown to be homozygous Pde6b rd1 carriers. Some presumably heterozygous carriers were identified among the 129/SvJ mice with normal ERG. The empty PCR control is indicated by a slash; arrow: expected size at 3.3 kb.
Figure 6.
 
Molecular analysis for the presence of the Pde6b rd1 allele. Genomic DNA of all mouse strains tested in this study was checked by PCR for the presence or absence of the Pde6b rd1 allele. C3HeB/FeJ mice as well as in 129/SvJblind mice with lowered ERG response were shown to be homozygous Pde6b rd1 carriers. Some presumably heterozygous carriers were identified among the 129/SvJ mice with normal ERG. The empty PCR control is indicated by a slash; arrow: expected size at 3.3 kb.
Figure 7.
 
Age-dependence of retinal development and ERG response. Histologic sections and the corresponding ERG is given for the age points 3.5, 4, 6, 8, 8.5, and 11 weeks.
Figure 7.
 
Age-dependence of retinal development and ERG response. Histologic sections and the corresponding ERG is given for the age points 3.5, 4, 6, 8, 8.5, and 11 weeks.
The authors thank Mareike Maurer for expert technical assistance and Thorsten Schwarz for help with data analysis. 
Krumpaszky HG, Klauss V. Epidemiology of blindness and eye disease. Ophthalmologica. 1996;210:1–84. [CrossRef] [PubMed]
Rivolta C, Sharon D, DeAngelis MM, Dryja TP. Retinitis pigmentosa and allied diseases: numerous diseases, genes, and inheritance patterns. Hum Mol Genet. 2002;11:1219–1227. [CrossRef] [PubMed]
Stone EM, Sheffield VC, Hageman GS. Molecular genetics of age-related macular degeneration. Hum Mol Genet. 2001;10:2285–2292. [CrossRef] [PubMed]
Allikmets R, Singh N, Sun H, et al. A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nat Genet. 1997;15:236–246. [CrossRef] [PubMed]
Bernstein PS, Tammur J, Singh N, et al. Diverse macular dystrophy phenotype caused by a novel complex mutation in the ELOV4 gene. Invest Ophthalmol Vis Sci. 2001;42:3331–3336. [PubMed]
Zhang K, Kniazeva M, Han M, et al. A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy. Nat Genet. 2001;27:89–93. [PubMed]
Petit C. Usher syndrome: from genetics to pathogenesis. Annu Rev Genomics Hum Genet. 2001;2:271–297. [CrossRef] [PubMed]
Weil D, Blanchard S, Kaplan J, et al. Defective myosin VIIa gene responsible for Usher syndrome type 1B. Nature. 1995;374:60–61. [CrossRef] [PubMed]
Verpy E, Leibovici M, Zwaenepoel I, et al. A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C. Nat Genet. 2000;26:51–55. [CrossRef] [PubMed]
Bork JM, Peters LM, Riazuddin S, et al. Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23. Am J Hum Genet. 2001;68:26–37. [CrossRef] [PubMed]
Ahmed ZM, Riazuddin S, Bernstein SL, et al. Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F. Am J Hum Genet. 2001;69:25–34. [CrossRef] [PubMed]
Weil D, El-Amraoui A, Masmoudi S, et al. Usher syndrome type I G (USH1G) is caused by mutations in the gene encoding SANS, a protein that associates with the USH1C protein, harmonin. Hum Mol Genet. 2003;12:463–471. [CrossRef] [PubMed]
Weston MD, Eudy JD, Fujita S, et al. Genomic structure and identification of novel mutations in Usherin, the gene responsible for Usher syndrome type IIa. Am J Hum Genet. 2000;66:1199–1210. [CrossRef] [PubMed]
Joensuu T, Hämäläinen R, Yuan B, et al. Mutations in a novel gene with transmembrane domains underlie Usher syndrome type 3. Am J Hum Genet. 2001;69:673–684. [CrossRef] [PubMed]
Fazzi E, Signorini SG, Scelsa B, Bova SM, Lanzi G. Leber’s congenital amaurosis: an update. Eur J Paediatr Neurol. 2003;7:13–22. [CrossRef] [PubMed]
Freund CL, Gregory-Evans CY, Furukawa T, et al. Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor. Cell. 1997;91:543–553. [CrossRef] [PubMed]
Cremers FPM, van de Pol DJR, van Driel M, et al. Autosomal recessive retinitis pigmentosa and cone-rod dystrophy caused by splice site mutations in the Stargardt’s disease gene ABCR. Hum Mol Genet. 1998;7:355–362. [CrossRef] [PubMed]
Kelsell RE, Gregory-Evans K, Payne AM, et al. Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy. Hum Mol Genet. 1998;7:1179–1184. [CrossRef] [PubMed]
Kohl S, Marx T, Giddings I, et al. Total colourblindness is caused by mutations in the gene encoding the α-subunit of the cone photoreceptor cGMP-gated cation channel. Nat Genet. 1998;19:257–259. [CrossRef] [PubMed]
Wissinger B, Gamer D, Jägle H, et al. CNGA3 mutations in hereditary cone photoreceptor disorders. Am J Hum Genet. 2001;69:722–737. [CrossRef] [PubMed]
Kohl S, Baumann B, Broghammer M, et al. Mutations in the CNGB3 gene encoding the β-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome 8q21. Hum Mol Genet. 2000;9:2107–2116. [CrossRef] [PubMed]
Pusch CM, Zeitz C, Brandau O, et al. The complete form of X-linked congenital stationary night blindness is caused by mutations in a gene encoding a leucine-rich repeat protein. Nat Genet. 2000;26:324–327. [CrossRef] [PubMed]
van den Hurk JAJM, Hendriks W, van de Pol DJR, et al. Mouse choroideremia gene mutation causes photoreceptor cell degeneration and is not transmitted through the female germline. Hum Mol Genet. 1997;6:851–858. [CrossRef] [PubMed]
Redmond TM, Yu S, Lee E, et al. Rpe65 is necessary for production of 11-cis vitamin A in the retinal visual cycle. Nat Genet. 1998;20:344–351. [CrossRef] [PubMed]
Quadro L, Blaner WS, Salchow DJ, et al. Impaired retinal function and vitamin A availability in mice lacking retinol-binding protein. EMBO J. 1999;18:4633–4644. [CrossRef] [PubMed]
Duncan JL, LaVail MM, Yasumura D, et al. An RCS-like retinal dystrophy phenotype in Mer knockout mice. Invest Ophthalmol Vis Sci. 2003;44:826–838. [CrossRef] [PubMed]
Biel M, Seeliger M, Pfeifer A, et al. Selective loss of cone function in mice lacking the cyclic nucleotide-gated channel CNG3. Proc Natl Acad Sci USA. 1999;96:7553–7557. [CrossRef] [PubMed]
Weng J, Mata NL, Azarian SM, Tzekov RT, Birch DG, Travis GH. Insights into the function of Rim protein in photoreceptors and etiology of Stargardt’s disease from the phenotype in abcr knockout mice. Cell. 1999;98:13–23. [CrossRef] [PubMed]
Xu J, Dodd RL, Makino CL, Simon MI, Baylor DA, Chen J. Prolonged photoresponses in transgenic mouse rods lacking arrestin. Nature. 1997;389:505–509. [CrossRef] [PubMed]
Furukawa T, Morrow EM, Li T, Davis FC, Cepko CL. Retinopathy and attenuated circadian entrainment in Crx-deficient mice. Nat Genet. 1999;23:466–470. [CrossRef] [PubMed]
Lem J, Krasnoperova NV, Calvert PD, et al. Morphological, physiological, and biochemical changes in rhodopsin knockout mice. Proc Natl Acad Sci USA. 1999;96:736–741. [CrossRef] [PubMed]
Chen CK, Burns ME, Spencer M, et al. Abnormal photoresponses and light-induced apoptosis in rods lacking rhodopsin kinase. Proc Natl Acad Sci USA. 1999;96:3718–3722. [CrossRef] [PubMed]
Clarke G, Goldberg AF, Vidgen D, et al. Rom-1 is required for rod photoreceptor viability and the regulation of disk morphogenesis. Nat Genet. 2000;25:67–73. [CrossRef] [PubMed]
Hong D-H, Pawlyk BS, Shang J, Sandberg MA, Berson EL, Li T. A retinitis pigmentosa GTPase regulator (RPGR)-deficient mouse model for X-linked retinitis pigmentosa (RP3). Proc Natl Acad Sci USA. 2000;97:3649–3654. [CrossRef] [PubMed]
Hagstrom SA, Duyao M, North MA, Li T. Retinal degeneration in tulp1 −/− mice: vesicular accumulation in the interphotoreceptor matrix. Invest Ophthalmol Vis Sci. 1999;40:2795–2802. [PubMed]
Seeliger MW, Biesalski HK, Wissinger B, et al. Phenotype in retinol deficiency due to a hereditary defect in retinol binding protein synthesis. Invest Ophthalmol Vis Sci. 1999;40:3–11. [PubMed]
Seeliger MW, Grimm C, Ståhlberg F, et al. New views on RPE65 deficiency: the rod system is the source of vision in a mouse model of Leber congenital amaurosis. Nat Genet. 2001;29:70–74. [CrossRef] [PubMed]
Pittler SJ, Baehr W. Identification of a nonsense mutation in the rod photoreceptor cGMP phosphodiesterase beta-subunit gene of the rd mouse. Proc Natl Acad Sci USA. 1991;88:8322–8326. [CrossRef] [PubMed]
Ma J, Norton JC, Allen AC, et al. Retinal degeneration slow (rds) in mouse results from simple insertion of a t haplotype-specific element into protein-coding exon II. Genomics. 1995;28:212–219. [CrossRef] [PubMed]
Burmeister M, Novak J, Liang MY, et al. Ocular retardation mouse caused by Chx10 homeobox null allele: impaired retinal progenitor proliferation and bipolar cell differentiation. Nat Genet. 1996;12:376–384. [CrossRef] [PubMed]
Chang B, Hawes NL, Hurd RE, Davisson MT, Nusinowitz S, Heckenlively JR. Retinal degeneration mutants in the mouse. Vision Res. 2002;42:517–525. [CrossRef] [PubMed]
Festing MFW. Origins and characteristics of inbred strains of mice. Lyon MF Rastan S Brown SDM eds. Genetic Variants and Strains of the Laboratory Mouse. 1996; 2nd ed. 1537–1576. Oxford University Press London.
Angeletti B, Löster J, Auricchio A, et al. An in vivo doxycycline-controlled expression system for functional studies of the retina. Invest Ophthalmol Vis Sci. 2003;44:755–760. [CrossRef] [PubMed]
Naka KI, Rushton WA. S-potentials from luminosity units in the retina of fish (Cyprinidae). J Physiol. 1966;185:587–599. [CrossRef] [PubMed]
Hasegawa S, Ohshima A, Hayakawa Y, Takagi M, Abe H. Multifocal electroretinograms in patients with branch retinal artery occlusion. Invest Ophthalmol Vis Sci. 2001;42:298–304. [PubMed]
Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;8476:307–310.
Bowes C, Li T, Frankel WW, et al. Localization of a retroviral element within the rd gene coding for the beta subunit of cGMP phosphodiesterase. Proc Natl Acad Sci USA. 1993;90:2955–2959. [CrossRef] [PubMed]
Li C, Cheng M, Yang H, Peachy NS, Naash MI. Age-related changes in the mouse outer retina. Optom Vis Sci. 2001;78:425–430. [CrossRef] [PubMed]
Fulton AB, Hansen RM, Findl O. The development of the rod photoresponse from dark-adapted rats. Invest Ophthalmol Vis Sci. 1995;36:1038–1045. [PubMed]
Jaissle GB, May CA, Reinhard J, et al. Evaluation of the Rhodopsin knockout mouse as a model of pure cone function. Invest Ophthalmol Vis Sci. 2001;42:506–513. [PubMed]
Simpson EM, Linder CC, Sargent EE, Davisson MT, Mobraaten LE, Sharp JJ. Genetic variation among 129 substrains and its importance for targeted mutagenesis in mice. Nat Genet. 1997;16:19–27. [CrossRef] [PubMed]
Threadgill DW, Yee D, Matin A, Nadeau JH, Magnuson T. Genealogy of the 129 inbred strains: 129/SvJ is a contaminated inbred strain. Mamm Genome. 1997;8:390–393. [CrossRef] [PubMed]
Figure 1.
 
Electroretinography on fixed, anesthetized mice. The handheld Ganzfeld stimulator is fixed at the bottom, and the mouse is moved on its sled into the position for examination with both eyes within the Ganzfeld bowl.
Figure 1.
 
Electroretinography on fixed, anesthetized mice. The handheld Ganzfeld stimulator is fixed at the bottom, and the mouse is moved on its sled into the position for examination with both eyes within the Ganzfeld bowl.
Figure 2.
 
Intensity series of corneal electroretinograms in one representative strain C57BL/6J mouse. (A) Traces show averages of 10 individual responses to a luminance of (1) 0.0125; (2) 0.025; (3) 0.125; (4) 0.5; (5) 1.25; (6) 5; (7) 12.5; (8) 50; (9) 125; and (10) 500 cd-s/m2. For screening purposes in all other groups, 5 and 125 cd-s/m2 were chosen as step 1 and step 2 (bold traces), respectively, to shorten examination times. (B) (♦) amplitudes of the b-waves. The line shows the Naka-Rushton fit in this mouse.
Figure 2.
 
Intensity series of corneal electroretinograms in one representative strain C57BL/6J mouse. (A) Traces show averages of 10 individual responses to a luminance of (1) 0.0125; (2) 0.025; (3) 0.125; (4) 0.5; (5) 1.25; (6) 5; (7) 12.5; (8) 50; (9) 125; and (10) 500 cd-s/m2. For screening purposes in all other groups, 5 and 125 cd-s/m2 were chosen as step 1 and step 2 (bold traces), respectively, to shorten examination times. (B) (♦) amplitudes of the b-waves. The line shows the Naka-Rushton fit in this mouse.
Figure 3.
 
RMS values in all mice in all groups. To detect mice with functional retinal impairment the RMS value of each group was compared with all other groups. The C3H and the 129/SvJblind strains showed statistically significant difference to all other normal groups in step 1. In step 2 these two groups were different from all other groups except for JF1. In addition, we found statistically significant differences of the RMS between the following normal strains in step 2: JF1 versus 102, JF1 versus AKR, JF1 versus CBA/CaJ, CBA/CaJ versus C57BL/6JIco, and CBA/CaJ versus DBA/2NCrlBR.
Figure 3.
 
RMS values in all mice in all groups. To detect mice with functional retinal impairment the RMS value of each group was compared with all other groups. The C3H and the 129/SvJblind strains showed statistically significant difference to all other normal groups in step 1. In step 2 these two groups were different from all other groups except for JF1. In addition, we found statistically significant differences of the RMS between the following normal strains in step 2: JF1 versus 102, JF1 versus AKR, JF1 versus CBA/CaJ, CBA/CaJ versus C57BL/6JIco, and CBA/CaJ versus DBA/2NCrlBR.
Figure 4.
 
Comparisons of left and right eye recordings by linear regression analysis. (A) Amplitude of step 1 of a- and b-waves (r = 0.729 and 0.408, respectively, both P < 0.0001), (B) amplitude of step 2 of a- and b-wave (r = 0.686 and 0.245, P < 0.0001 and < 0.05, respectively), (C) implicit time of step 1 of a- and b-wave (r = 0.867 and 0.919, respectively, both P < 0.0001), (D) implicit time of step 2 of a- and b-wave (r = 0.954 and 0.942, respectively, both P < 0.0001).
Figure 4.
 
Comparisons of left and right eye recordings by linear regression analysis. (A) Amplitude of step 1 of a- and b-waves (r = 0.729 and 0.408, respectively, both P < 0.0001), (B) amplitude of step 2 of a- and b-wave (r = 0.686 and 0.245, P < 0.0001 and < 0.05, respectively), (C) implicit time of step 1 of a- and b-wave (r = 0.867 and 0.919, respectively, both P < 0.0001), (D) implicit time of step 2 of a- and b-wave (r = 0.954 and 0.942, respectively, both P < 0.0001).
Figure 5.
 
The ERG response corresponded to retinal histology. The ERG response of one mouse is given together with the histology of its retina. The mouse strains used are C57BL/6J, C57BL/6JIco, C3HeB/FeJ, 129/SvJblind, 129/SvJ, CBA/CaJ, DBA/2NCrlBR, 102, and AKR. GCL, ganglion cell layer; INL, inner nuclear layer; IPL, inner plexiform layer; PE, pigmented epithelium; OFL, outer fiber layer; ONL, outer nuclear layer; OPL, outer plexiform layer.
Figure 5.
 
The ERG response corresponded to retinal histology. The ERG response of one mouse is given together with the histology of its retina. The mouse strains used are C57BL/6J, C57BL/6JIco, C3HeB/FeJ, 129/SvJblind, 129/SvJ, CBA/CaJ, DBA/2NCrlBR, 102, and AKR. GCL, ganglion cell layer; INL, inner nuclear layer; IPL, inner plexiform layer; PE, pigmented epithelium; OFL, outer fiber layer; ONL, outer nuclear layer; OPL, outer plexiform layer.
Figure 6.
 
Molecular analysis for the presence of the Pde6b rd1 allele. Genomic DNA of all mouse strains tested in this study was checked by PCR for the presence or absence of the Pde6b rd1 allele. C3HeB/FeJ mice as well as in 129/SvJblind mice with lowered ERG response were shown to be homozygous Pde6b rd1 carriers. Some presumably heterozygous carriers were identified among the 129/SvJ mice with normal ERG. The empty PCR control is indicated by a slash; arrow: expected size at 3.3 kb.
Figure 6.
 
Molecular analysis for the presence of the Pde6b rd1 allele. Genomic DNA of all mouse strains tested in this study was checked by PCR for the presence or absence of the Pde6b rd1 allele. C3HeB/FeJ mice as well as in 129/SvJblind mice with lowered ERG response were shown to be homozygous Pde6b rd1 carriers. Some presumably heterozygous carriers were identified among the 129/SvJ mice with normal ERG. The empty PCR control is indicated by a slash; arrow: expected size at 3.3 kb.
Figure 7.
 
Age-dependence of retinal development and ERG response. Histologic sections and the corresponding ERG is given for the age points 3.5, 4, 6, 8, 8.5, and 11 weeks.
Figure 7.
 
Age-dependence of retinal development and ERG response. Histologic sections and the corresponding ERG is given for the age points 3.5, 4, 6, 8, 8.5, and 11 weeks.
Table 1.
 
Bland-Altman Analysis of Amplitude and Implicit Time of Right and Left Eyes in Steps 1 and 2
Table 1.
 
Bland-Altman Analysis of Amplitude and Implicit Time of Right and Left Eyes in Steps 1 and 2
Amplitude (μV) Implicit Time (ms)
a-Wave b-Wave a-Wave b-Wave
Step 1 Step 2 Step 1 Step 2 Step 1 Step 2 Step 1 Step 2
Average of all eyes −11.2 −33.1 140.3 162.2 28.3 26.7 99.1 79.9
Mean of right-left eye 1.4 1.6 2.9 −8.3 −0.3 −0.2 −0.3 −0.4
SD of right-left eye 4.3 12.4 42.9 52.0 3.6 1.9 7.2 10.1
Percentage of eyes within 2 SD-range 95.1 95.2 93.8 96.9 92.7 95.2 92.3 93.8
Table 2.
 
ERG Parameters of Each Normal Group
Table 2.
 
ERG Parameters of Each Normal Group
Group a-Wave b-Wave
Step 1 Step 2 Step 1 Step 2
Amplitude [μV]
 102 −12.2 ± 3.3 −27.7 ± 12.6 137.6 ± 10.9 165.3 ± 10.7
 129/SvJ −12.6 ± 4.7 −22.5 ± 10.0 124.0 ± 35.9 159.1 ± 46.5
 AKR −11.1 ± 2.1 −38.5 ± 15.0 163.5 ± 21.0 177.8 ± 17.0
 C57BL/6J −10.5 ± 3.4 −41.6 ± 8.6 148.9 ± 36.1 179.2 ± 9.8
 C57BL/6Jlco −7.9 ± 4.5 −39.8 ± 17.5 148.3 ± 38.7 172.1 ± 46.1
 CBA/CaJ −12.9 ± 5.3 −20.7 ± 11.6 145.6 ± 27.2 167.6 ± 28.8
 DBA/2NCrlBR −10.9 ± 7.3 −32.4 ± 7.1 119.2 ± 14.7 132.3 ± 14.2
 JF1 −13.5 ± 7.2 −36.1 ± 7.5 120.6 ± 31.9 126.5 ± 15.7
Implicit time [ms]
 102 23.4 ± 5.6 26.4 ± 3.0 110.8 ± 11.3 92.1 ± 14.5
 129/SvJ 23.5 ± 7.5 26.4 ± 3.6 102.4 ± 8.4 80.0 ± 7.4
 AKR 25.7 ± 2.1 25.7 ± 1.7 81.6 ± 5.9 69.6 ± 8.0
 C57BL/6J 28.3 ± 9.2 25.9 ± 2.2 103.3 ± 17.8 72.4 ± 7.1
 C57BL/6Jlco 29.6 ± 5.9 28.6 ± 5.5 98.2 ± 13.2 75.2 ± 9.0
 CBA/CaJ 24.0 ± 3.5 22.1 ± 3.9 107.5 ± 12.9 91.8 ± 19.5
 DBA/2NCrlBR 30.5 ± 4.3 29.8 ± 2.0 92.8 ± 15.5 75.2 ± 10.1
 JF1 36.2 ± 4.0 29.6 ± 3.5 90.1 ± 10.6 61.4 ± 4.1
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×