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 dystrophy and an allelic variant of the mdx mouse (mdxCv3) have been shown to be abnormal. Analysis of five allelic variants of the mdx mouse with mutations in the dystrophin gene has shown that there is a correlation 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 antibodies on retinal sections from three allelic mdx mouse strains, we have examined the localization of each of the isoforms. We show that Dp71 expression does not overlap with Dp427 and Dp260 expression at the outer plexiform layer (OPL). Instead, Dp71 is localized to the inner limiting membrane (ILM) and to retinal blood vessels. Moreover, we show that Dp260 and Dp71 differ structurally at their respective C-termini. In addition, we find that the proper localization of the beta-dystroglycan is dependent upon both Dp260 at the OPL and Dp71 expression at the ILM. Thus, Dp260 and Dp71 are non-redundant isoforms that are located at different sites within the retina yet have a common interaction with beta-dystroglycan. Our data suggest that both Dp71 and Dp260 contribute distinct but essential roles to retinal electrophysiology.
Howard
P L
PL
Department of Medical and Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Dally
G Y
GY
Wong
M H
MH
Ho
A
A
Weleber
R G
RG
Pillers
D A
DA
Ray
P N
PN
D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D016189:Dystrophin / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D004596:Electroretinography; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D008969:Molecular Sequence Data; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000503:physiopathology; D009154:Mutation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D012160:Retina / Q000502:physiology*
D000906:Antibodies; D016189:Dystrophin; D011993:Recombinant Fusion Proteins