Mapping quantitative trait loci for hearing loss in Black Swiss mice

Abstract

In common inbred mouse strains, hearing loss is a highly prevalent quantitative trait, which is mainly controlled by the Cdh23 753 A variant and alleles at numerous other strain-specific loci. Here, we investigated the genetic basis of hearing loss in non-inbred strains. Mice of Swiss Webster, CF-1, NIH Swiss, ICR, and Black Swiss strains exhibited hearing profiles characteristic of progressive, sensorineural hearing impairment. In particular, CF-1, Black Swiss, and NIH Swiss mice showed early-onset hearing impairment, ICR and Swiss Webster mice expressed a delayed-onset hearing loss, and NMRI mice had normal hearing. By quantitative trait locus (QTL) mapping, two significant QTLs were identified underlying hearing loss in Black Swiss mice: one QTL mapped to chromosome (chr) 10 (named ahl5, LOD 8.9, peak association 35–42 cM) and a second QTL localized to chr 18 ( ahl6, LOD 3.8, 38–44 cM). Ahl5 and ahl6 account for 61% and 32% of the variation in the backcross, respectively. Cadherin 23 ( Cdh23) and protocadherin 15 ( Pcdh15), mapping within the 95% confidence interval of ahl5, bear nucleotide polymorphisms in coding exons, but these appear to be unrelated to the hearing phenotype. Haplotype analyses across the Cdh23 locus demonstrated the phylogenetic relationship between Black Swiss and common inbred strains.