Structural and functional rescue of murine rod photoreceptors by human rhodopsin transgene

Citation
N. Mcnally et al., Structural and functional rescue of murine rod photoreceptors by human rhodopsin transgene, HUM MOL GEN, 8(7), 1999, pp. 1309-1312
Citations number
16
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
HUMAN MOLECULAR GENETICS
ISSN journal
0964-6906 → ACNP
Volume
8
Issue
7
Year of publication
1999
Pages
1309 - 1312
Database
ISI
SICI code
0964-6906(199907)8:7<1309:SAFROM>2.0.ZU;2-1
Abstract
Mice carrying a targeted disruption of the rhodopsin gene develop a severe degenerative retinopathy, failing to elaborate rod photoreceptor outer segm ents (ROS), having no recordable rod electroretinogram (ERG) and losing all of their rod cells over a period of similar to 12 weeks. Murine and human rhodopsins differ in their amino acid sequences, Whether, or to what extent , such variability might influence the ability of human rhodopsin to serve as an adequate structural and functional substitute for the endogenous prot ein in mouse rod cells bears direct relevance to exploiting the full utilit y of Rho(-/-) animals as a model of degenerative retinal disease in man. We crossed Rho(-/-) mice with mice expressing a wild-type human rhodopsin tra nsgene at levels approximating to those of the endogenous protein, Immunohi stological examination of retinal selections from such animals demonstrated ROS of normal number and length and temporal expression of rhodopsin simil ar to that observed in wild-type animals; that is, immunoreactivity to an a nti-rhodopsin antibody became clearly evident by day 3 post-partum. Whereas Rho(-/-) mice never display a rod ERG response, and even lose cone respons es by 12 weeks of age, rescued mice showed 75% normal maximum amplitudes an d had ERG b-wave thresholds (based on a 50 mu V criterion) within 0.1 log u nit of normal wild-type at 20 weeks, and cone amplitudes remained normal at this age. These data demonstrate very substantial structural and functiona l rescue of the rod photoreceptors of Rho(-/-) mice and long-term preservat ion by the human rhodopsin transgene.