A major gene affecting age-related hearing loss is common to at least ten inbred strains of mice

Inbred strains of mice offer promising models for understanding the genetic basis of human presbycusis or age-related hearing loss (AHL), We previousl y mapped a major gene affecting AHL in C57BL/6J mice. Here, we show that th e same Chromosome 10 gene (Ahl) is a major contributor to AHL in nine other inbred mouse strains-129P1/ReJ, A/J, BALB/cByJ, BUB/BnJ, C57BR/cdJ, DBA/2J , NOD/LtJ, SKH2/J, and STOCK760. F1 hybrids between each of these inbred st rains and the normal-hearing inbred strain CAST/Ei retain good hearing, ind icating that inheritance of AHL is recessive. To follow segregation of hear ing loss, F1 hybrids were backcrossed to the parental strains with AHL. Aud itory-evoked brain-stem response thresholds were used to assess hearing in more than 1500 N2 mice and analyzed as quantitative traits for linkage asso ciations with Chromosome 10 markers. Highly significant linkage was found i n all nine strain backcrosses, with the highest probability (LOD > 70) near the marker DIOMit112 This map position for Ahl is near the waltzer mutatio n (v) and the modifier of deaf waddler locus (mdfw), suggesting the possibi lity of allelism. Results from an intercross of C57BL/6J and NOD/LtJ mice i ndicate that the 6- to 10-month difference in AHL onset between these two s trains is not due to allelic heterogeneity of the Ahl gene. (C) 2000 Academ ic Press.