Genetically engineered large animal model for studying cone photoreceptor survival and degeneration in retinitis pigmentosa

Nat Biotechnol. 1997 Oct;15(10):965-70. doi: 10.1038/nbt1097-965.

Abstract

Patients with retinitis pigmentosa (RP) typically develop night blindness early in life due to loss of rod photoreceptors. The remaining cone photoreceptors are the mainstay of their vision; however, over years or decades, these cones slowly degenerate, leading to blindness. We created transgenic pigs that express a mutated rhodopsin gene (Pro347Leu). Like RP patients with the same mutation, these pigs have early and severe rod loss; initially their cones are relatively spared, but these surviving cones slowly degenerate. By age 20 months, there is only a single layer of morphologically abnormal cones and the cone electroretinogram is markedly reduced. Given the strong similarities in phenotype to that of RP patients, these transgenic pigs will provide a large animal model for study of the protracted phase of cone degeneration found in RP and for preclinical treatment trials.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Blotting, Southern
  • Disease Models, Animal
  • Electroretinography
  • Embryo Transfer
  • Gene Expression Regulation / genetics
  • Genetic Engineering
  • Microscopy, Electron
  • Molecular Sequence Data
  • Phenotype
  • Polymerase Chain Reaction
  • Retina / pathology
  • Retina / physiopathology*
  • Retina / ultrastructure
  • Retinal Cone Photoreceptor Cells / physiopathology*
  • Retinal Cone Photoreceptor Cells / ultrastructure
  • Retinal Degeneration / physiopathology
  • Retinitis Pigmentosa / genetics*
  • Retinitis Pigmentosa / physiopathology
  • Rhodopsin / chemistry
  • Rhodopsin / genetics
  • Swine / embryology
  • Swine / genetics*
  • Transgenes

Substances

  • Rhodopsin

Associated data

  • GENBANK/AF008947