title: Transgenic mice with a rhodopsin mutation (Pro23His): a mouse model of autosomal dominant retinitis pigmentosa.
abstract: 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.
authors.affiliation: Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston 02114.
authors.forename: J E
authors.initials: JE
authors.lastname: Olsson
authors.forename: J W
authors.initials: JW
authors.lastname: Gordon
authors.forename: B S
authors.initials: BS
authors.lastname: Pawlyk
authors.forename: D
authors.initials: D
authors.lastname: Roof
authors.forename: A
authors.initials: A
authors.lastname: Hayes
authors.forename: R S
authors.initials: RS
authors.lastname: Molday
authors.forename: S
authors.initials: S
authors.lastname: Mukai
authors.forename: G S
authors.initials: GS
authors.lastname: Cowley
authors.forename: E L
authors.initials: EL
authors.lastname: Berson
authors.forename: T P
authors.initials: TP
authors.lastname: Dryja
mesh_terms: D000818:Animals; D003062:Codon; D004195:Disease Models, Animal; D004596:Electroretinography; D005654:Fundus Oculi; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009154:Mutation; D009887:Ophthalmoscopy; D010786:Photoreceptor Cells / Q000737:chemistry; D011392:Proline / Q000235:genetics*; D015183:Restriction Mapping; D012160:Retina / Q000473:pathology / Q000503:physiopathology; D012171:Retinal Vessels / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D012243:Rhodopsin / Q000235:genetics*; D017299:Rod Opsins / Q000032:analysis / Q000235:genetics
chemical_list: D003062:Codon; D017299:Rod Opsins; D012243:Rhodopsin; D011392:Proline