Inactivation of the murine X-linked juvenile retinoschisis gene, Rs1h, suggests a role of retinoschisin in retinal cell layer organization and synaptic structure

Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6222-7. doi: 10.1073/pnas.092528599.


Deleterious mutations in RS1 encoding retinoschisin are associated with X-linked juvenile retinoschisis (RS), a common form of macular degeneration in males. The disorder is characterized by a negative electroretinogram pattern and by a splitting of the inner retina. To gain further insight into the function of the retinoschisin protein and its role in the cellular pathology of RS, we have generated knockout mice deficient in Rs1h, the murine ortholog of the human RS1 gene. We show that pathologic changes in hemizygous Rs1h(-/Y) male mice are evenly distributed across the retina, apparently contrasting with the macula-dominated features in human. Similar functional anomalies in human and Rs1h(-/Y) mice, however, suggest that both conditions are a disease of the entire retina affecting the organization of the retinal cell layers as well as structural properties of the retinal synapse.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Northern
  • Blotting, Western
  • Cells, Cultured
  • Electrophysiology
  • Electroretinography
  • Eye Proteins / genetics*
  • Eye Proteins / physiology*
  • Genetic Vectors
  • Mice
  • Mice, Knockout
  • Microscopy, Electron
  • Microscopy, Fluorescence
  • Mutation*
  • Ophthalmoscopy
  • Retina / cytology*
  • Retina / metabolism*
  • Synapses / metabolism*


  • Eye Proteins
  • RS1 protein, human