1C-10 Multiple susceptive loci on chromosome 5 affecting early onset haring loss of in DBA/2J mice

The ahl1 locus is an important contributor to age-related hearing loss (AHL) in many inbred mouse strains and was shown to be a strain-specific dimorphism of Cadherin 23 (Cdh23). DBA/2J (D2) mice show severe hearing loss for high frequencies and begin to lose hearing by 2 month of age for mid-frequencies, much earlier than other Cdh23ahl1 homozygous strains. These data indicate that additional genetic factors contribute to the early-onset hearing loss (EHL) of D2 mice. To investigate the genetic factors of EHL in D2 mice, we perfumed linkage analysis. This approach showed strong evidence for at least four susceptive loci on chromosome 5. These loci associations with lod scores above 3.0 were detected. One of their QTLs was mapped close to ahl2 locus that associates with hearing loss of NOD/LtJ (NOD) mice. To prove whether hearing loss between D2 and NOD mice associate with same locus, we tested the mutation for complementation using by (D2 X NOD) F1 mice. Although the all F1 mice showed the severe hearing loss at 8 weeks, the hearing levels are middle range between D2 and NOD mice. Therefore, the major locus affecting hearing loss of D2 mice is not allelic with ahl2 in NOD mice.