Profiling Photoreceptor and Retinal Disease Candidate Genes with the Tg01 Transgenic Mouse Line

Abstract

Abstract: : Purpose:To profile photoreceptor–enriched genes and to select candidate genes for hereditary retinal diseases by using the Tg01 transgenic mouse line, which lacks photoreceptor development in the ventral retina (Fong S.–L. et al. IOVS 2003; 44:ARVO Abstract 4516). Methods: Four groups of total RNA were prepared from dorsal and ventral retinas of transgenic and non–transgenic mice. Each group contained four repeated samples. A total of sixteen samples were analyzed separately on individual Affymetrix Mouse Genome MOE430A microarrays. Results: By comparing the expressed genes in dorsal and ventral retinas of transgenic and non–transgenic mice and choosing different parameters including p–values and fold changes, 1,349 photoreceptor–enriched, 883 rod–enriched and 634 cone–enriched genes were identified from 22,690 genes on microarray. Thirty one photoreceptor–specific genes involved in phototransduction and hereditary retinal diseases were compared with the selected lists of photoreceptor–enriched, rod–enriched and cone–enriched genes, all of them (except the RP1 gene) were found in the aforementioned gene lists. Taking advantage of the known chromosomal locations and the information generated from Human Genome Project, candidate genes for the hereditary retinal diseases with unknown causes were selected. Most of the diseases had less than 10 candidate genes. Nevertheless, the following ten cases, RP6, RP17, RP22, RP24, RP29, CORD1, CORD9, CYMD, ARMD1 and MCDR3 had less than three candidate genes for each disease. Among the six genes that are known to be expressed in both rod and cone photoreceptors, four of them, Gucy2E, RGS9, rhodopsin kinase and retinoschisin were found in both rod– and cone–enriched gene lists, but the other two, GCAP1 and recoverin only were found in rod–enriched gene list. Of additional interest, the comparison of expression for short–wave and medium–wave opsin genes in dorsal and ventral retinas confirmed the uneven distribution of these cone visual pigments that is known to occur in the mouse retina. Conclusions: The Tg01 mouse is an ideal system for profiling photoreceptor–enriched, rod–enriched and cone–enriched genes. The information obtained could be used to select candidate genes for hereditary retinal diseases.

Keywords: candidate gene analysis • retinal degenerations: hereditary • transgenics/knock–outs