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 dystr ophy and an allelic variant of the mdx mouse (mdx(Cv3)) have been show n to be abnormal. Analysis of five allelic variants of the mdx mouse w ith mutations in the dystrophin gene has shown that there is a correla tion between the position of the mutation and the severity of the ERG abnormality. Three isoforms are expressed in the retina: Dp427, Dp260 and Dp71, Using indirect immunofluorescence and isoform-specific antib odies on retinal sections from three allelic mdx mouse strains, we hav e examined the localization of each of the isoforms, We show that Dp71 expression does not overlap with Dp427 and Dp260 expression at the ou ter plexiform layer (OPL). Instead, Dp71 is localized to the inner lim iting membrane (ILM) and to retinal blood vessels. Moreover, we show t hat Dp260 and Dp71 differ structurally at their respective C-termini, In addition, we find that the proper localization of the beta-dystrogl ycan is dependent upon both Dp260 at the OPL and Dp71 expression at th e ILM. Thus, Dp260 and Dp71 are non-redundant isoforms that are locate d at different sites within the retina yet have a common interaction w ith beta-dystroglycan. Our data suggest that both Dp71 and Dp260 contr ibute distinct but essential roles to retinal electrophysiology.