Transgenic mice with a rhodopsin mutation (Pro23His): a mouse model of autosomal dominant retinitis pigmentosa.
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.
Olsson
J E
JE
Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston 02114.
Gordon
J W
JW
Pawlyk
B S
BS
Roof
D
D
Hayes
A
A
Molday
R S
RS
Mukai
S
S
Cowley
G S
GS
Berson
E L
EL
Dryja
T P
TP
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
D003062:Codon; D017299:Rod Opsins; D012243:Rhodopsin; D011392:Proline