| First Author | Chang B | Year | 2024 |
| Journal | MGI Direct Data Submission | Mgi Jnum | J:346129 |
| Mgi Id | MGI:7614441 | Citation | Chang B (2024) The Rpe65 |
| abstractText | The spontaneous mutation rd12-2J was discovered in our ocular phenotypes screening program in two male F2 mice from a linkage cross between B6.SJL(C)-Slc25a13hspn/Kjn and CAST/EiJ. Those two male F2 mice had a severely diminished electroretinogram (ERG) at 1 month of age and the ERG phenotype could be bred away from the spinning and deafness phenotypes of Slc25a13hspn. We mated the mutant males with C57BL/6J and all F1 mice had normal ERGs proving the phenotype recessive. Linkage crosses then showed this spontaneous mutation to be an autosomal recessive mutation that maps to Chromosome 3 in the same location as the rd12 mutation of Rpe65. We did a complementation test between this new mutant and Rpe65rd12, and the result was positive. cDNA sequence analysis of this new mutant did not find a mutation in the coding sequence of Rpe65 but the failed complementation with rd12 proved them allelic and we have assigned this new mutation the allele symbol Rpe65rd12-2J for retinal degeneration 12, 2 Jackson. We developed a C57BL/6J congenic strain, B6.Cg-Rpe65rd12-2J/Boc (JAX Stock No. 035328), by backcrossing the Rpe65rd12-2J allele from one of the original F2 mapping cross males onto C57BL/6J for 7 generations then sibling mating to homozygosity. Rod electroretinogram assessment of homozygotes at 1 month of age showed a diminished a-wave and b-wave (dark adapted responses) and cone electroretinogram assessment showed time-delayed b-wave (Figure 1). Because this phenotype is so reliable at 1 month of age, ERG was used to select homozygotes for breeding at each generation of the backcross. The retinal white dots and degeneration phenotypes are very similar in B6.Cg-Rpe65rd12-2J/Boc (Stock No. 035328) (Figure 2B) compared with B6(A)-Rpe65rd12/J (Jax Stock No. 005379) at 5 months of age (Figure 2C). This mutant has been suggested as a model for the human Leber congenital amaurosis 2 (LCA2) and retinitis pigmentosa 20 (RP20). |
