Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  10
• Reference
  J:241137 Johnson KR, et al., Effects of Cdh23 single nucleotide substitutions on age-related hearing loss in C57BL/6 and 129S1/Sv mice and comparisons with congenic strains. Sci Rep. 2017 Mar 13;7:44450
• ID
  MGI:5904373

Genes

Gene	Assay Type
Mahl	reported elsewhere

Notes

• Experiment
  A single nucleotide variant (SNV) of the cadherin 23 gene (Cdh23^c.753), common to many inbred mouse strains, accelerates age-related hearing loss (AHL) and can worsen auditory phenotypes of other mutations. Homologous recombination in C57BL/6NJ (B6N) and 129S1/SvImJ (129S1) embryonic stem cells was used to engineer mouse strains with reciprocal single base pair substitutions B6N(Cg)-Cdh23^tm2.1Kjn/Kjn (B6-Cdh23^c.753AG) and 129.Sv-Cdh23^tm1.1Kjn/Kjn (129S1-Cdh23^c.753GA).
  
  ABR thresholds and cochlear pathologies of these SNV mice with those of congenic B6.129S1-(rs13480546-rs13480629)/Kjn (B6.129S1-Cdh23^Ahl/+) and 129S1.B6-(rs3696307-rs257098870)/Kjn (129S1.B6-Cdh23^ahl) and parental(B6N and 129S1) strain mice were compared.
  
  Results verified the protective effect of the Cdh23^c.753G allele, which
  prevented high frequency hearing loss in B6 mice to at least 18 months of age, and the AHL-inducing effect of the Cdh23^c.753A allele, which worsened hearing loss in 129S1 mice. ABR thresholds differed between 129S-Cdh23^c.753A SNV and 129S1.B6-Cdh23^ahl congenic mice, and a linkage backcross involving these strains localized a Chr 10 QTL contributing to the difference.
  
  A total of 182 N2 generation progeny were produced from the backcross, and each mouse was assessed for ABR thresholds at three months of age and genotyped for 13 SNPs that differ between B6 and 129S1 strain DNA and that span the 20-70Mb region of Chr 10. SNP marker genotypes were used to assign haplotypes to individual N2 mice to better define the 129S1.B6-Cdh23^ahl congenic region and to identify informative crossover events to further refine the Mahl candidate gne region.
  
  Allelic segregation analysis identified a locus within the Chr 10 congenic region of 129S1.B6-Cdh23^ahl that strongly associated with the hearing loss variation observed in the N2 progeny. The locus was designated Mahl for its modifying effect on the hearing loss of 129S1 mice homozygous for the Cdh23^c.753A(ahl) variant. The Mahl candidate gene region was narrowed to a 5 Mb interval between rs13480619 and rs29330969 that included the Cdh23 gene on Chr 10 [Figure 6.C.].