Abstract
Abstract: :
Purpose: Enhanced S–cone syndrome, or Goldman–Favre syndrome, is caused by mutations in the retinal transcription factor NR2E3. The molecular pathways leading to the establishment of the disease phenotype and the genes regulated by NR2E3 have not yet been identified. The purpose of this study was to determine which genes are under the influence of NR2E3 by comparing gene expression patterns before and after the onset of NR2E3 expression, around embryonic day 18, in a mouse strain (rd7) lacking functional NR2E3 to those of normal control mice. Methods: Embryonic mouse eyes were obtained at E17.5 and E19.5 from several litters of rd7 as well as C57/BL6 control mice. RNA was extracted and utilized for gene array analysis using Affymetrix 430A gene chips. Expression patterns were determined independently on days E17.5 and E19.5 for both rd7 and control animals and analyzed. Results: Many genes which are functionally related to cell growth and maintenance, cell to cell communication, morphogenesis and protein metabolism were expressed in similar temporal patterns in rd7 and normal mice, e.g. the genes Kcna5, Ptgds and Thra are only transcribed at E19.5 in both strains. In contrast, a significant number of genes that were either activated or deactivated between E17.5 and E19.5 in normal animals failed to do so in rd7 mice, remaining either silent or maintaining transcription throughout this period. The precise function of many of these genes is not known. However, a considerable fraction of the genes differentially expressed in rd7 mice appear to be involved in the regulation of transcription activity or the organization of the microtubule cytoskeleton. Examples of genes that remained silent in rd7 mice but were expressed in control animals include Gna13, Tpm3, Tcte3, and Rab2. Conclusions: Our results suggest that while the majority of all gene expression changes observed in the mouse retina between E17.5 and E19.5 are independent of the presence of NR2E3, the expression of some ocular genes requires the presence of NR2E3 during embryogenesis. Further study of the functional properties of these genes may not only reveal the pathogenesis of enhanced S–cone syndrome but may also reveal the mechanisms involved in the normal development of the retinal cytoarchitecture.
Keywords: degenerations/dystrophies • retinal development • gene/expression