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K Cheon, J Gao, S Nusinowitz, Q Liu, D Bei, K Atkins, A AzimiRP1 Consortium, J Zuo; Progressive Photoreceptor Degeneration, Outer Segment Dysplasia and Rhodopsin Mislocalization in Mice with Targeted Disruption of the Retinitis Pigmentosa-1 (Rp1) Gene . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3667.
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Purpose: Retinitis Pigmentosa (RP) is one of the most prevalent groups of retinopathies in humans. Mutations in the recently identified photoreceptor specific gene RP1 account for 5-10% of autosomal dominant RP cases. We investigated the mechanism of role of Rp1 protein and retinal degeneration in RP1 disease in this study. Methods: We generated a mouse model of the RP1 form of RP by targeted disruption of the mouse orthologue (Rp1) of the human RP1 gene. Results: Homozygous mutant mice (Rp1-/-) exhibited progressive degeneration of rod photoreceptors. However, the number of cones did not significantly decrease up to 10 months. Light and electron microscopy demonstrated that outer segments in both Rp1-/- rods and cones were abnormal in morphology and progressively shortened in length. Rhodopsin, the most abundant rod outer segment protein, was mislocalized in inner segments and cell bodies of Rp1-/- rods prior to cell death. ERG of Rp1-/- mice was significantly reduced compared to that of Rp1+/+ mice, whereas that of Rp1+/- mice was at an intermediate level. Conclusion: These findings demonstrate that Rp1 is required for normal morphogenesis of photoreceptor outer segments. Rp1 may also play a role in rhodopsin transport to the outer segment . Characteristics of the phenotypes of Rp1 mutant mice resemble those of the human RP1 disease, and these mice provide a model for investigating the pathogenesis of this devastating disease.
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