Dystrophin and beta-dystroglycan in photoreceptor terminals from normal and mdx(3Cv) mouse retinae

Mutations in the dystrophin gene cause muscular dystrophy as well as cognit ive impairments, including an abnormal dark-adapted electroretinogram. To i nvestigate the basis for the ocular phenotype, we analysed dystrophin and t he dystrophin-associated protein beta-dystroglycan in retinae from mdx(3Cv) mice, This strain has a mutation in the dystrophin gene and abnormalities in the electroretinogram which are similar to those of muscular dystrophy p atients. Despite an overall reduction of all dystrophin isoforms and of bet a-dystroglycan in retinal tissue from mutant mice, we observed no apparent change in the histotypic layering of the retina, or in the ultrastructure o f several specific cell types, including rods and cones. In retinae from wi ld type and mdx(3Cv) mice, dystrophin and beta-dystroglycan were concentrat ed in small extensions of rod and cone photoreceptor terminals protruding i nto the outer plexiform layer. Beta-dystroglycan but not dystrophin was als o clustered around the inner limiting membrane and the capillary basal lami nae. While the labelling pattern around the basal laminae was not altered i n the mutant mice, we found that the area as well as the intensity of the d ystrophin and beta-dystroglycan immunoreactivity associated with the termin als of rod photoreceptors were severely reduced. The same parameters were m uch less affected in cone terminals. These results show, that dystrophin an d beta-dystroglycan are differentially distributed in the retina, and that a severe reduction of dystrophin has no gross effect on retinal structure, but could influence intraretinal signalling at the level of the photorecept or terminals. Moreover, the mutation in mdx(3Cv) mice has a selective effec t on rods, providing an explanation for the altered electroretinogram.