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.

FVB/NJ Mice Demonstrate a Youthful Sensitivity to Noise-Induced Hearing Loss and Provide a Useful Genetic Model for the Study of Neural Hearing Loss

“…The OBN noise exposure was previously described [White et al, 2009]. During exposure, mice were housed in a circular ¼ inch wire-mesh exposure cage with four pie shaped compartments and were permitted to move about within the compartment.…”

“…We are able to exploit the evidence that there are genetic and environmental factors influencing ARHI and NIHL [Friedman et al, 2009; White et al, 2009]. Recently, genome wide association studies (GWAS) have been employed to discover genes conferring susceptibility to complex traits in humans.…”

Alleles that modulate late life hearing in genetically heterogeneous mice

“…A number of genetic loci have been identified that modulate the rate of hearing loss or the sensitivity to noise (White et al, 2009) and several that modulate both age and noise effects (Ohlemiller, 2006), suggesting common genetic features underlying each form of pathology. A complication in interpreting most previous genetic studies, however, is their reliance on inbred mouse strains, each of which consists entirely of individuals of a single genotype, and in which all loci have been forced to homozygosity.…”

Large-scale phenotyping of noise-induced hearing loss in 100 strains of mice

“…Strains with PTS<20 at all frequencies were considered noise-resistant, whereas strains with PTS ≥20 at any frequency were considered noise-sensitive. A cutoff of 20dB was determined based on usage by prior studies [14,15]. Noise-sensitivities at each frequency were further categorized as mild (20≤PTS<30dB), moderate (30≤PTS<40dB), or severe (≥40dB).…”