Progressive retinal degeneration and dysfunction in R6 Huntington's disease mice.
Huntington's disease (HD) and spinocerebellar ataxia type 7 (SCA7) belong to a group of progressive neurodegenerative diseases caused by polyglutamine (polyQ) expansions. SCA7 is the only one to display degeneration in the retina, a tissue usually spared in HD. We previously described a SCA7 transgenic retinal model expressing mutant full length ataxin-7 in rod photoreceptors. These mice develop a severe and characteristic retinopathy. We show here that R6 transgenic mice, which reproduce many features of HD, express mutant huntingtin in the retina leading to strong vision deficiencies and retinal dystrophy. These two different polyQ mouse models exhibit comparable early and progressive retinal degeneration and dysfunction. These abnormalities are reminiscent of other retinal degeneration phenotypes (in particular rd7/rd7 mice) where photoreceptor cell loss occurs. Retinopathy in R6 and R7E models can be monitored in living mice by ERG and fundus examination, which can facilitate in vivo evaluation of therapeutic agents in polyQ disorders.
Helmlinger
Dominique
D
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, B.P.10142, 67404 ILLKIRCH Cedex, CU de Strasbourg, France.
Yvert
Gaël
G
Picaud
Serge
S
Merienne
Karine
K
Sahel
José
J
Mandel
Jean-Louis
JL
Devys
Didier
D
D000818:Animals; D000906:Antibodies / Q000276:immunology; D015153:Blotting, Western; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000503:physiopathology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012160:Retina / Q000473:pathology; D012162:Retinal Degeneration / Q000503:physiopathology*
D000906:Antibodies; C086055:HTT protein, human; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins