Survey of the nob5 mutation in C3H substrains

PURPOSE: A no b-wave (nob) electroretinography (ERG) phenotype arose spontaneously in a colony of C3H mice and was named nob5. A mutation was identified in the Gpr179 gene in homozygous nob5 mice. There is a concern that this mutation is also present in additional C3H sublines and may compromise retinal research performed using these lines. In this report, therefore, we provide a phenotype and genotype survey of nob5 in six C3H substrains present at the Jackson Laboratory. METHODS: Fundus changes were evaluated in the six C3H substrains with image-guided optical coherence tomography (OCT), and retinal function was assessed with ERG. The substrains were genotyped with PCR using appropriate primers for the nob5 mutation. Additionally, the genomic sequences of C3H/HeJ, available from the Jackson Laboratory, and C3H/HeH, available from the Wellcome Trust Sanger Institute, were examined for the Gpr179(nob5) mutation. RESULTS: Two C3H congenic strains, C3Sn.BLiA-Pde6b(+)/DnJ and C3A.BLiA-Pde6b(+)/J, wild-type for Pde6b, used as the sighted control strains and had normal fundi, OCT, and ERG responses. Four C3H strains C3H/HeJ, C3HeB/FeJ, C3H/HeOuJ, and C3H/HeSnJ bearing the Pde6b(rd1) allele exhibited a grainy fundus appearance, retinal degeneration on OCT, and no rod and cone ERG responses. The nob5 mutation was not observed in the six C3H strains assessed with PCR genotyping. Further, the genomic sequences of C3H/HeJ and C3H/HeH did not contain the nob5 mutation. CONCLUSIONS: The Gpr179(nob5) allele is not present in C3H substrains at the Jackson Laboratory. Therefore, the usefulness of these C3H strains as commonly used models to study the effects of photoreceptor degeneration is not compromised.