title: Genome-wide screening for genetic loci associated with noise-induced hearing loss.
abstract: Noise-induced hearing loss (NIHL) is one of the more common sources of environmentally induced hearing loss in adults. In a mouse model, Castaneous (CAST/Ei) is an inbred strain that is resistant to NIHL, while the C57BL/6J strain is susceptible. We have used the genome-tagged mice (GTM) library of congenic strains, carrying defined segments of the CAST/Ei genome introgressed onto the C57BL/6J background, to search for loci modifying the noise-induced damage seen in the C57BL/6J strain. NIHL was induced by exposing 6-8-week old mice to 108 dB SPL intensity noise. We tested the hearing of each mouse strain up to 23 days after noise exposure using auditory brainstem response (ABR). This study identifies a number of genetic loci that modify the initial response to damaging noise, as well as long-term recovery. The data suggest that multiple alleles within the CAST/Ei genome modify the pathogenesis of NIHL and that screening congenic libraries for loci that underlie traits of interest can be easily carried out in a high-throughput fashion.
authors.affiliation: Department of Cell Biology and Genetics, House Ear Institute, Gonda Center for Cellular and Molecular Biology, 2100 West 3rd Street, Los Angeles, CA 90057, USA. cwhite@hei.org
authors.forename: Cory H
authors.initials: CH
authors.lastname: White
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Ohmen
authors.forename: Sonal
authors.initials: S
authors.lastname: Sheth
authors.forename: Amina F
authors.initials: AF
authors.lastname: Zebboudj
authors.forename: Richard K
authors.initials: RK
authors.lastname: McHugh
authors.forename: Larry F
authors.initials: LF
authors.lastname: Hoffman
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.forename: Richard C
authors.initials: RC
authors.lastname: Davis
authors.forename: Rick A
authors.initials: RA
authors.lastname: Friedman