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B Chang, NL Hawes, RE Hurd, MT Davisson, S Nusinowitz, JR Heckenlively; A Point Mutation in the Rpe65 Gene Causes Retinal Degeneration (rd12) in Mice . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3670.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To report the clinical appearance, histology, chromosomal localization, and mutant gene identification of a new hereditary model of retinal degeneratio (rd12). Methods: We characterized the clinical effects of this mutation using serial indirect ophthalmoscopy, fundus photography, electroretinography (ERG), and histology, and performed genetic analysis including linkage studies and gene identification. Results: Mice homozygous for the rd12 mutation show retinal spots at 7 months of age with retinal degeneration starting at 12 months of age. Despite the relatively late onset of retinal degeneration in the rd12 homozygous mutant mice, their eyes show a poor rod and good cone ERG response at 3 weeks of age. Genetic analysis showed that rd12 is an autosomal recessive mutation and maps to mouse Chromosome 3 closely linked to D3Mit19, suggesting that the human homolog may be on Chromosome 1p31 where the human RPE65 gene is located. Sequence analysis shows that the retinal degeneration is caused by a nonsense mutation in exon 3 of the Rpe65 gene and the gene symbol for the rd12 mutation has been changed to Rpe65rd12. Conclusion: Mutations in the retinal pigment epithelium gene encoding RPE65 are a cause of an early-onset autosomal recessive form of human retinitis pigmentosa (RP), known as Leber congenital amaurosis (LCA), that results in blindness or severely impaired vision in children. The natural arising rd12 mutation will provide a good model for studying the pathogenesis of autosomal recessive retinitis pigmentosa (arRP) in human.
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