| First Author | Chang B | Year | 2024 |
| Journal | MGI Direct Data Submission | Mgi Jnum | J:347037 |
| Mgi Id | MGI:7620509 | Citation | Chang B (2024) The no b wave 11 mutation. MGI Direct Data Submission |
| abstractText | The spontaneous mutation no b wave 11 (nob11) was discovered in a female of STOCK Hcn4tm2.1(cre/ERT2)Sev/J (JAX Stock No. 024283) in 2017 as part of our ocular phenotypes screening program. She had significantly elevated ERG thresholds (Rod b-wave=787 µV, cone b-wave =340 µV), but her male mate had a normal ERG response (rod b-wave=316 µV, cone b-wave=181 µV). We mated this mutant female to a DBA/2J male for the linkage cross and the F1 mice had a normal ERG, proving this a recessive mutation. In the F2 mice, we discovered that only one F1 mating pair produced approximately 25% F2 mice with no rod ERG b-wave and a greatly reduced cone ERG, and we named this new ERG phenotype as nob11. Because of the phenotype we did a complementation test between this new ERG phenotype nob11 and nob3 (B6.B10(D2)-Grm6nob3/BocJ, JAX Stock No. 016883), but the result was negative. The F2 population of the mapping cross to DBA/2J mapped nob11 to mouse Chromosome 7 between markers D7Mit145 and D7Mit66, suggesting that the Trpm1 gene was the best candidate in the region. We then did a complementation test between nob11 and Trpm1rd15 and the result was positive proving nob11 to be an allele of Trpm1. We made a congenic line by tracking the retinal phenotype of nob11 through backcross-intercross to C57BL/6J for 5 cycles of backcrossing, assessing the ERG phenotype in the intercross generations at 3 to 4 weeks of age to identify homozygous breeders. Then we sibling intercrossed to make a homozygous congenic strain for nob11. Mice homozygous for the nob11 mutation show a normal fundus and OCT (Figure 1A) at 1 month of age and some retinal white spots and normal OCT at 6 months of age (Figure 1B), but no rod ERG b-wave and a much-reduced cone ERG by 4 weeks of age. Mutations in TRPM1 cause autosomal recessive complete congenital stationary night blindness-1C (CSNB1C) in human and the B6.Cg-Trpm1nob11/Boc strain (JAX Stock No. 036964) should be another good mouse model for human CSNB1C. Acknowledgment: This work was supported by National Institutes of Health grant 5R01EY019943. |
