Dystrophin and beta-dystroglycan in photoreceptor terminals from normal and mdx3Cv mouse retinae

Eur J Neurosci. 1999 Jun;11(6):2121-33. doi: 10.1046/j.1460-9568.1999.00636.x.

Abstract

Mutations in the dystrophin gene cause muscular dystrophy as well as cognitive impairments, including an abnormal dark-adapted electroretinogram. To investigate the basis for the ocular phenotype, we analysed dystrophin and the dystrophin-associated protein beta-dystroglycan in retinae from mdx3Cv mice. This strain has a mutation in the dystrophin gene and abnormalities in the electroretinogram which are similar to those of muscular dystrophy patients. Despite an overall reduction of all dystrophin isoforms and of beta-dystroglycan in retinal tissue from mutant mice, we observed no apparent change in the histotypic layering of the retina, or in the ultrastructure of several specific cell types, including rods and cones. In retinae from wild type and mdx3Cv mice, dystrophin and beta-dystroglycan were concentrated in small extensions of rod and cone photoreceptor terminals protruding into the outer plexiform layer. Beta-dystroglycan but not dystrophin was also clustered around the inner limiting membrane and the capillary basal laminae. While the labelling pattern around the basal laminae was not altered in the mutant mice, we found that the area as well as the intensity of the dystrophin and beta-dystroglycan immunoreactivity associated with the terminals of rod photoreceptors were severely reduced. The same parameters were much less affected in cone terminals. These results show, that dystrophin and 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 photoreceptor terminals. Moreover, the mutation in mdx3Cv mice has a selective effect on rods, providing an explanation for the altered electroretinogram.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cytoskeletal Proteins / metabolism*
  • Dystroglycans
  • Dystrophin / metabolism*
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred mdx / anatomy & histology
  • Mice, Inbred mdx / metabolism*
  • Microscopy, Electron
  • Nerve Endings / metabolism*
  • Photoreceptor Cells, Vertebrate / metabolism*
  • Reference Values
  • Retina / cytology
  • Retina / metabolism*
  • Retina / pathology
  • Retinal Rod Photoreceptor Cells / pathology
  • Tissue Distribution / physiology

Substances

  • Cytoskeletal Proteins
  • Dystrophin
  • Membrane Glycoproteins
  • Dystroglycans