title: Ahl2, a second locus affecting age-related hearing loss in mice.
abstract: Inbred mouse strains with age-related hearing loss (AHL) provide valuable models for studying the genetic basis of human presbycusis. Here we report the genetic mapping of a second AHL locus in mice (designated Ahl2) that is a major contributor to the 8- to 10-month difference in hearing loss onset times between NOD/LtJ and C57BL/6J mice. A whole-genome linkage scan of 110 progeny from a (C57BL/6JxNOD/LtJ)xNOD/LtJ backcross revealed statistically significant associations of ABR thresholds with markers on chromosome 5, with a peak lod score of 5.5 for D5Mit309. At 6 months of age, backcross progeny that inherited two copies of the recessive NOD/LtJ-derived allele at this locus (genotype ahl2/ahl2) exhibited ABR thresholds that were on average 26 decibels above those of heterozygous mice. Analysis of a (CAST/EixNOD/LtJ)xNOD/LtJ backcross, which segregates strain-specific alleles at both Ahl2 and the Ahl locus on chromosome 10, showed that the hearing loss attributable to Ahl2 is dependent on a predisposing Ahl genotype. The statistically significant effect of Ahl2 observed in crosses with NOD/LtJ was not seen in crosses involving three other strains with early onset AHL: A/J, BUB/BnJ, and SKH2/J.
authors.affiliation: The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine, 04609, USA. krj@jax.org
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Johnson
authors.forename: Qing Yin
authors.initials: QY
authors.lastname: Zheng
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D008040:Genetic Linkage; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010641:Phenotype; D011304:Presbycusis / Q000235:genetics*; D040641:Quantitative Trait Loci