Localization of dystrophin isoform Dp71 to the inner limiting membrane of the retina suggests a unique functional contribution of Dp71 in the retina

The electroretinograms (ERGs) of patients with Duchenne muscular dystrophyand an allelic variant of the mdx mouse (mdxCv3) have been shown to beabnormal. Analysis of five allelic variants of the mdx mouse with mutationsin the dystrophin gene has shown that there is a correlation between theposition of the mutation and the severity of the ERG abnormality. Threeisoforms are expressed in the retina: Dp427, Dp260 and Dp71. Using indirectimmunofluorescence and isoform-specific antibodies on retinal sections fromthree allelic mdx mouse strains, we have examined the localization of eachof the isoforms. We show that Dp71 expression does not overlap with Dp427and Dp260 expression at the outer plexiform layer (OPL). Instead, Dp71 islocalized to the inner limiting membrane (ILM) and to retinal bloodvessels. Moreover, we show that Dp260 and Dp71 differ structurally at theirrespective C-termini. In addition, we find that the proper localization ofthe beta- dystroglycan is dependent upon both Dp260 at the OPL and Dp71expression at the ILM. Thus, Dp260 and Dp71 are non-redundant isoforms thatare located at different sites within the retina yet have a commoninteraction with beta-dystroglycan. Our data suggest that both Dp71 andDp260 contribute distinct but essential roles to retinal electrophysiology.