Transgenic mice with a rhodopsin mutation (Pro23His): a mouse model of autosomal dominant retinitis pigmentosa

Neuron. 1992 Nov;9(5):815-30. doi: 10.1016/0896-6273(92)90236-7.


We inserted into the germline of mice either a mutant or wild-type allele from a patient with retinitis pigmentosa and a missense mutation (P23H) in the rhodopsin gene. All three lines of transgenic mice with the mutant allele developed photoreceptor degeneration; the one with the least severe retinal photoreceptor degeneration had the lowest transgene expression, which was one-sixth the level of endogenous murine rod opsin. Of two lines of mice with the wild-type allele, one expressed approximately equal amounts of transgenic and murine opsin and maintained normal retinal function and structure. The other expressed approximately 5 times more transgenic than murine opsin and developed a retinal degeneration similar to that found in mice carrying a mutant allele, presumably due to the overexpression of this protein. Our findings help to establish the pathogenicity of mutant human P23H rod opsin and suggest that overexpression of wild-type human rod opsin leads to a remarkably similar photoreceptor degeneration.

Publication types

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

MeSH terms

  • Animals
  • Codon
  • Disease Models, Animal*
  • Electroretinography
  • Fundus Oculi
  • Humans
  • Mice
  • Mice, Transgenic
  • Microscopy, Electron
  • Mutation*
  • Ophthalmoscopy
  • Photoreceptor Cells / chemistry
  • Proline / genetics*
  • Restriction Mapping
  • Retina / pathology
  • Retina / physiopathology
  • Retinal Vessels / pathology
  • Retinitis Pigmentosa / genetics*
  • Retinitis Pigmentosa / pathology
  • Retinitis Pigmentosa / physiopathology
  • Rhodopsin / genetics*
  • Rod Opsins / analysis
  • Rod Opsins / genetics


  • Codon
  • Rod Opsins
  • Rhodopsin
  • Proline