Ahl2, a Second Locus Affecting Age-Related Hearing Loss in Mice

• Published in: Genomics (San Diego, Calif.) Calif.), 2002-11, Vol.80 (5), p.461-464
• Main Authors: Johnson, Kenneth R., Zheng, Qing Yin
• Format: Article
• Language: English
• Subjects: Aging - pathology; Animals; Biological and medical sciences; Chromosome Mapping; Crosses, Genetic; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; Genes. Genome; Genetic Linkage; Genotype; Hearing Loss - genetics; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Molecular and cellular biology; Molecular genetics; Phenotype; Presbycusis - genetics; Quantitative Trait Loci
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.2002.6858

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/6J×NOD/LtJ)×NOD/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/Ei×NOD/LtJ)×NOD/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.