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Ahl3, a third locus on mouse chromosome 17 affecting age-related hearing loss
Authors:Nemoto M  Morita Y  Mishima Y  Takahashi S  Nomura T  Ushiki T  Shiroishi T  Kikkawa Y  Yonekawa H  Kominami R
Institution:Department of Molecular Genetics, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi 1-757, Niigata 951-8122, Japan.
Abstract:Genetic variation in humans probably plays a role in determining the range of individual susceptibility to age-related hearing loss (AHL), but no contributing loci have been identified because of the difficulties of dissecting complex traits in humans. This paper reports mapping of an AHL locus using a panel of consomic mice between C57BL/6J (B6) and MSM strains, which covered more than a half of chromosome sets. B6 strain exhibited AHL beginning at 10 months of age whereas MSM strain, derived from Japanese wild mice, had normal hearing throughout life. Individuals in the panel were examined with auditory brainstem response (ABR) at various months of age, revealing that one particular strain (B6-Chr17(MSM)) substituting the chromosome 17 with the MSM-derived one showed a prominent resistance, having still good hearing at 18 months of age. Subsequent mapping using 89 individuals in the cross between B6-Chr17(MSM) and B6 was performed, which showed a significant association of ABR thresholds with loci in the vicinity of D17Mit119. These results show a novel AHL-resistant locus, designated as Ahl3, on the chromosome 17.
Keywords:Age-related hearing loss  Consomic strain  QTL  Genetic mapping  ABR
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