Journal
GENOMICS
Volume 92, Issue 4, Pages 219-225Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygeno.2008.06.007
Keywords
presbycusis; age-related hearing loss; progressive hearing loss; inbred strains of mice; DBA; auditory brainstem response; chromosome mapping; quantitative trait loci; QTL; complex trait genetics
Funding
- National Institutes of Health (NIH) [DC005827]
- National Institute on Deafness and Other Communication Disorders
- NIH National Cancer Institute [CA34196]
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The DBA/2J inbred strain of mice is used extensively in hearing research, yet little is known about the genetic basis for its early onset, progressive hearing loss. To map underlying genetic factors we analyzed recombinant inbred strains and linkage backcrosses. Analysis of 213 mice from 31 BXD recombinant inbred strains detected linkage of auditory brain-stem response thresholds with a locus on distal chromosome 11, which we designate ahl8. Analysis of 225 N2 mice from a backcross of (C57BL/6J x DBA/2J) F1 hybrids to DBA/2J mice confirmed this linkage (LOD > 50) and refined the ahl8 candidate gene interval. Analysis of 214 mice from a backcross of (B6.CAST-Cdh23(Ahl+) x DBA/2J) F1 hybrids to DBA/2J mice demonstrated a genetic interaction of Cdh23 with ahl8. We conclude that ahl8 is a major contributor to the hearing loss of DBA/2J mice and that its effects are dependent on the predisposing Cdh23(ahl) genotype of this strain. (C) 2008 Elsevier Inc. All rights reserved.
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