Identification of a photoreceptor-specific mRNA encoded by the gene responsible for retinal degeneration slow (rds)

Abstract

MUTANT mice homozygous for 'retinal degeneration slow' (rds/rds) are characterized phenotypically by abnormal development of photoreceptor outer segments in the retina, followed by gradual degeneration of photoreceptors^1–3. This process of degeneration is complete by one year, with preservation of all other retinal cells⁴. The biochemical defect that leads to the mutant phenotype is not known. Our strategy for cloning the rds gene was based upon three previously reported observations. First, the rds locus maps to chromosome 17^5,6. Second, experimental rds/rds ↦+/+ and rds/+ ↦ +/+ tetra-parental mice manifest patchy photoreceptor changes in the retina^7,8 suggesting that the wild-type rds locus is expressed within cells of the photoreceptor lineage. Finally, the process of degeneration is specific to photore-ceptors. On the basis of these observations, we predicted that the rds mRNA is encoded by a gene on chromosome 17 and is normally expressed exclusively within photoreceptors in the retina. We here present evidence that this is the case.