RETINAL DEGENERATION IN THE RD MOUSE IN THE ABSENCE OF C-FOS

PURPOSE. Apoptosis is the final common death pathway of photoreceptors in light-induced retinal degeneration and in several animal models fo r retinal dystrophy. To date, little is known about gene regulation of apoptosis in the retina. The expression of the immediate early gene c -fos is upregulated concomitant with apoptosis in light-induced photor eceptor degeneration and in the rd mouse, an animal model for inherite d retinal degeneration. In a recent study it was shown that c-Fos is e ssential for light-induced apoptosis of photoreceptors in vivo. To det ermine whether c-Fos is also involved in the apoptotic pathway of inhe rited retinal degeneration, rd/rd, c-fos(-/-) double-mutant mice have been generated. METHODS. Double-mutant mite (rd/rd, c-fos(-/-)) were c rossbred from c-fos(+/-) mice and rd/rd mice. Their genotype was deter mined by polymerase chain reaction analysis of genomic DNA. Wild-type control mice and homozygous rd mice were killed at 2-day intervals fro m postnatal day (P)9 through P21. Double-mutant mice were killed at po stnatal days P9, P11, P13, P15, and P21. To determine levels of apopto sis in the retina, eyes were enucleated and processed for light micros copy and in situ nick-end labeling. Total retinal DNA was extracted fr om isolated retinas for DNA fragmentation analysis. RESULTS. Morpholog ic, histochemical, and biochemical analyses showed that the time cours e of apoptosis and the outcome of photoreceptor degeneration in rd/rd, c-fos(-/-) double-mutant mice was indistinguishable from that in rd m ice carrying functional c-fos. CONCLUSIONS. These data suggest that in contrast to its role in light-induced photoreceptor degeneration, c-F os is not essential for apoptosis in the rd mouse.