This point substitution of asparagine in place of a conserved isoleucine in the last of seven transmembrane domains of rhodopsin makes heterozygotes highly sensitive to light-induced photoreceptor degeneration, although there is no loss of photoreceptor cell bodies at 1 year of age when maintained in standard housing conditions without bright light exposure. This provides a slightly less severe model of Retinitis Pigmentosa 4 than the RhoTvrm1 allele.
Read More +Genetic Background | Generation |
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000664 C57BL/6J |
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Allele Type | Gene Symbol | Gene Name |
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Chemically induced (ENU) (Not Specified) | Rho | rhodopsin |
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RhoTvrm4 heterozygotes are highly sensitive to light-induced photoreceptor degeneration, but when maintained in standard conditions with ambient light no loss of photoreceptor cell bodies was detected at 1 year of age and immunohistochemistry showed proper localization of rhodopsin to the outer segments. At 4 months of age the outer segment lengths are normal but at 1 year they are slightly shorter. Assessment by dark-adapted ERG found no reduction in the amplitude of alpha or beta waves in heterozygotes at 4 months or 1 year of age. Light-adapted ERGs also found no statistically significant abnormalities in beta wave amplitude. However, within one hour after a five-minute exposure to 12,000 lux of bright light the photoreceptor outer segment appears disorganized, there are areas either devoid of outer segments or having aggregates, and the apical processes of retinal pigment epithelium appear to extend further along the outer segments than normal. After 24 hours of exposure the inner and outer segments of the retina are disorganized, the border between them indiscernible, and apoptotic photoreceptor cells can be identified by TUNEL staining. One week after exposure photoreceptor degeneration has progressed extensively so that only 2 or fewer layers of photoreceptor nuclei remain. A two-minute exposure to 12,000 lux was found to be adequate to induce photoreceptor degeneration in two of three heterozygotes. Phototransduction deactivation is similar to that of wild-type controls in a two-flash ERG protocol, but heterozygotes have deficits in recovery of the a-wave from bleaching light.
The RhoTvrm4 mutation was induced by ethylnitrosourea in an ES cell derived from (129S4/SvJae x C57BL/6J)F1and backcrossed onto the C57BL/6J background by repeated cycles of backcrossing.
Allele Name | translational research vision model 4 |
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Allele Type | Chemically induced (ENU) (Not Specified) |
Allele Synonym(s) | I307N Rho |
Gene Symbol and Name | Rho, rhodopsin |
Gene Synonym(s) | |
Strain of Origin | (129S4/SvJae x C57BL/6J)F1 |
Chromosome | 6 |
Molecular Note | A missense mutation changes amino acid 307, isoleucine (ATC), to asparagine (AAC). Ile-307 is located in the 7th transmembrane region of RHO and is conserved across species, including human, primate, cat, dog, and rat. |
When using the Tvrm4 mouse strain in a publication, please cite the originating article(s) and include JAX stock #029087 in your Materials and Methods section.
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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