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 studied 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 determined by in situ hybridization with a transgene-specific RNA probe. Photoreceptors 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 of normal and transgenic photoreceptors displayed uniform but slower degeneration than that observed in a transgenic mouse of the same age. Our results demonstrate non-autonomy of gene action for the mutated rhodopsin gene and imply that cellular interactions between photoreceptors in the retina probably play a role in degeneration.
Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710.
P C
PC
Huang
A E
AE
Gaitan
Y
Y
Hao
R M
RM
Petters
F
F
Wong
D000595:Amino Acid Sequence; D000818:Animals; D002678:Chimera; D003433:Crosses, Genetic; D005260:Female; D005838:Genotype; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009030:Mosaicism; D010641:Phenotype; D010786:Photoreceptor Cells / Q000473:pathology*; D017354:Point Mutation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D012243:Rhodopsin / Q000235:genetics / Q000502:physiology*
D012333:RNA, Messenger; D012243:Rhodopsin