Generation and analysis of transgenic mice expressing P216L-substituted rds/peripherin in rod photoreceptors
| Autor: | W, Kedzierski, M, Lloyd, D G, Birch, D, Bok, G H, Travis |
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| Rok vydání: | 1997 |
| Předmět: |
Membrane Glycoproteins
Retinal Degeneration Peripherins Gene Expression Mice Transgenic Nerve Tissue Proteins Mice Mutant Strains Mice Inbred C57BL Disease Models Animal Mice Phenotype Intermediate Filament Proteins Retinal Rod Photoreceptor Cells Electroretinography Animals Transgenes Eye Proteins Microscopy Immunoelectron DNA Primers |
| Zdroj: | Investigative ophthalmologyvisual science. 38(2) |
| ISSN: | 0146-0404 |
| Popis: | 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.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.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.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. |
| Databáze: | OpenAIRE |
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