| First Author | Chang B | Year | 2024 |
| Mgi Jnum | J:348730 | Mgi Id | MGI:7643874 |
| Citation | Chang B (2024) The retinal degeneration 24 (rd24) mutation. |
| abstractText | The retinal degeneration 24 (rd24) heritable mutant phenotype was discovered in our ocular phenotypes screening program in June 2019 in strain NOD.Cg-Rag1tm1Mom Fancaem1Dvs Il2rgtm1Wjl/SzJ (JAX Stock No. 026062) that presented with progressive retinal degeneration at 6 months of age (Figure 1B), but the fundus was normal at 1 month of age (Figure 1B). In September 2019, the same retinal phenotype was discovered in NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl Tg(SLC10A1)15Mvw/MvwJ (JAX Stock No. 030533). The common ancestor for these two strains is NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl/SzJ (JAX Stock No. 007799), so we obtained more mice at different ages of NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl/SzJ and we discovered that this strain was fixed homozygous for the rd24 mutation. We did a complementation test between these three strains, and the result was positive. We mated the mutant from Stock No. 026062 with C57BL/6J and all F1 mice had normal retinas. The retinal degeneration phenotype was recovered in the F2 generation and this F2 generation was used as our linkage cross. The linkage cross confirmed that rd24 is an autosomal recessive mutation and it mapped on mouse Chromosome 5 closely linked to D5Mit356 with no crossover in 100 F2 mice. The best candidate gene in the region is Cnga1 (cyclic nucleotide gated channel alpha 1). We developed a C57BL/6J (B6) congenic strain, B6.Cg-rd24/Boc (JAX Stock No. 036968), by backcross-intercross breeding the rd24 allele from Stock No. 026062 onto C57BL/6J to NE5 then sibling mating to homozygosity. Mice homozygous for rd24 on this C57BL/6J background exhibit no rod derived ERG a-wave and attenuated ERG b-wave at 1 month of age, whereas the cone derived ERG responses are only slightly lower than normal. The retinal function decreases with age and there are no detectable ERG responses at 12 months of age (Figure 2, ERGs). OCT and Histology at 4 months of age showed approximately 60% photoreceptor loss (Figure 2B, C), but the fundus and OCT was normal at 1 month of age (Figure 1A and Figure 2A). Mutations in CNGA1 cause autosomal recessive retinitis pigmentosa 49 (RP49) in human and a progressive retinal degeneration in mice (Kandaswamy et al., 2022). Although the underlying molecular mutation remains to be defined, the rd24 mutant provides a new mouse model for human retinitis pigmentosa 49. |
