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W Kedzierski, M Lloyd, D G Birch, D Bok, G H Travis; Generation and analysis of transgenic mice expressing P216L-substituted rds/peripherin in rod photoreceptors.. Invest. Ophthalmol. Vis. Sci. 1997;38(2):498-509.
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© ARVO (1962-2015); The Authors (2016-present)
PURPOSE: In this study, the authors present the biochemical, morphologic, and physiological analyses of a transgenic mouse model for retinal degeneration slow (RDS)-mediated retinitis pigmentosa caused by a proline 216 to leucine (P216L) amino acid substitution in rds/peripherin. METHODS: The authors assembled a mutant rds transgene that encodes rds/peripherin with a P216L substitution. Transgenic mice were generated on wild-type (+/+), heterozygous (rds-/+), and homozygous (rds-/rds-) null genetic backgrounds. These mice were analyzed biochemically, by light and electron microscopy, and by electroretinography. RESULTS: In P216L-transgenic mice on a +/- background, the authors observed expression-level-dependent photoreceptor degeneration and outer-segment shortening. Expression of the P216L transgene on an rds-/+ background resulted in more severe photoreceptor degeneration and outer-segment dysplasia than seen in nontransgenic rds-/+ mutants. Severely dysplastic outer segments were detectable in P216L transgenics on an rds-/rds-null background. The reduction in b-wave amplitudes by electroretinography were well correlated with the degree of photoreceptor degeneration, but not outer-segment dysplasia in these different rds mutants. CONCLUSIONS: The phenotype in P216L-transgenic mice on an rds-/+ genetic background probably is caused by a combination of two genetic mechanisms: a direct dominant effect of the P216L substituted protein, and a reduction in the level of normal rds/peripherin. The expression pattern of the normal and mutant genes in these animals is similar to that predicted for humans with RDS-mediated autosomal-dominant retinitis pigmentosa. These mice may thus be considered an animal model for this disease.
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