CELLULAR INTERACTIONS IMPLICATED IN THE MECHANISM OF PHOTORECEPTOR DEGENERATION IN TRANSGENIC MICE EXPRESSING A MUTANT RHODOPSIN GENE

Photoreceptors of transgenic mice expressing a mutant rhodopsin gene ( Pro347 --> Ser) slowly degenerate. The mechanism of degeneration was s tudied by aggregation of embryos of normal and transgenic mice to form chimeras. In these chimeras, mosaicism was observed in the coat color , retinal pigment epithelium, and retina. In the retina, the genotype of adjacent patches of normal and transgenic photoreceptors was determ ined by in situ hybridization with a transgene-specific RNA probe. Pho toreceptors in the chimeric retina degenerated uniformly, independent of the genotype and similar to the photoreceptors in transgenic mice. However, the chimeric retinas showed varying proportions of normal and transgenic cells. The chimeric retina with a nearly even proportion o f normal and transgenic photoreceptors displayed uniform but slower de generation than that observed in a transgenic mouse of the same age. O ur results demonstrate non-autonomy of gene action for the mutated rho dopsin gene and imply that cellular interactions between photoreceptor s in the retina probably play a role in degeneration.