Knock-in human rhodopsin-GFP fusions as mouse models for human disease and targets for gene therapy.

Abstract:

:The human rhodopsin gene is the locus for numerous alleles linked to the neurodegenerative disease retinitis pigmentosa. To facilitate the study of retinal degeneration and to test reagents designed to alter the structure and function of this gene, we have developed strains of mice whose native rhodopsin gene has been replaced with the corresponding human DNA modified to encode an enhanced GFP fusion at the C terminus of rhodopsin. The human rhodopsin-GFP fusion faithfully mimics the expression and distribution of wild-type rhodopsin in heterozygotes and serves as a sensitive reporter of rod-cell structure and integrity. In homozygotes, however, the gene induces progressive retinal degeneration bearing many of the hallmarks of recessive retinitis pigmentosa. When the gene is flanked by recognition sites for Cre recombinase, protein expression is reduced approximately 5-fold despite undiminished mRNA levels, suggesting translation inhibition. GFP-tagged human rhodopsin provides a sensitive method to monitor the development of normal and diseased retinas in dissected samples, and it offers a noninvasive means to observe the progress of retinal degeneration and the efficacy of gene-based therapies in whole animals.

authors

Chan F,Bradley A,Wensel TG,Wilson JH

doi

10.1073/pnas.0403149101

keywords:

subject

Has Abstract

pub_date

2004-06-15 00:00:00

pages

9109-14

issue

24

eissn

0027-8424

issn

1091-6490

pii

0403149101

journal_volume

101

pub_type

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