Mapping Data

Experiment

• Experiment
  TEXT-Genetic Cross
• Chromosome
  13
• Reference
  J:97534 Johnson KR, et al., The Mass1(frings) mutation underlies early onset hearing impairment in BUB/BnJ mice, a model for the auditory pathology of Usher syndrome IIC. Genomics. 2005 May;85(5):582-90
• ID
  MGI:3581698

Genes

Gene	Allele
Adgrv1	Adgrv1^frings
D13Mit9

Notes

• Experiment
  Inbred strain BUB/BnJ exhibits signs of age related hearing loss starting at 3 weeks of age. This phenotype was mapped using 76 animals from a (CAST/Ei x BUB/BnJ)F1 x BUB/BnJ backcross and animals from a (MOLD/RkJ x BUB/BnJ)F1 x BUB/BnJ backcross. Animals were tested at different months to track hearing loss progression.
  
  Significant linkage to early hearing loss (before 6 months of age) mapped to 45 cM on mouse Chromosome 13 near D13Mit9 (LOD=12.6). This locus accounts for 80% of the phenotypic variation at 5 months of age. D13Mit9 is located in the Gpr98 gene. The Gpr98^frings mutation causes audiogenic seizures in Swiss albino mice, and the same mutation is also found in BUB/BnJ mice. Therefore it is thought that the Gpr98^frings mutation is responsible for early hearing loss in the BUB/BnJ inbred strain. BUB/BnJ exhibits susceptibility to audiogenic seizures but only when tested before 25 days of age unlike Gpr98^frings mice, which are seizures susceptible into adulthood. The human ortholog of Gpr98 is associated with Usher syndrome type IIC, which is characterized by sensorineural hearing loss and retinitis pigmentosa in female patients. Analysis of the backcross animals did not reveal a sex differential effect for Gpr98 genotype and the hearing loss phenotype. The effect of Gpr98 on retinitis pigmentosa could not be evaluated because BUB/BnJ carries an independent mutation for retinal degeneration (Pde6b^rd1).
  
  A previously identified age-related hearing loss locus, Cdh23, at 30 cM on mouse Chromosome 10 near D10Mit138 showed linkage to high-frequency pure tones in mice older than 10 months of age (LOD=6.9). This locus accounts for 15% of the phenotypic variation. Sequence analysis revealed that the BUB/BnJ inbred strain carries the Cdh23^ahlhearing loss susceptibility allele whereas the Mass1^frings strain carries the resistance allele at Cdh23. Taken together, Gpr98 and Cdh23 loci in backcross animals account for 75-85% of the phenotypic variation at all ages tested. Animals homozygous for Gpr98^frings and Cdh23^ahl exhibit the severe hearing loss by 5 months of age.