Genetic basis for susceptibility to noise-induced hearing loss in mice

Abstract

The C57BL/6J (B6) and DBA/2J (D2) inbred strains of mice exhibit an age-related hearing loss (AHL) due to a recessive gene ( Ahl) that maps to Chromosome 10. The Ahl gene is also implicated in the susceptibility to noise-induced hearing loss (NIHL). The B6 mice ( Ahl/Ahl) are more susceptible to NIHL than the CBA/CaJ (CB) mice (+ Ahl). The B6×D2.F 1 hybrid mice ( Ahl/Ahl) are more susceptible to NIHL than the CB×B6.F 1 mice (+/ Ahl) [Erway et al., 1996. Hear. Res. 93, 181–187]. These genetic effects implicate the Ahl gene as contributing to NIHL susceptibility. The present study demonstrates segregation for the putative Ahl gene and mapping of such a gene to Chromosome 10, consistent with other independent mapping of Ahl for AHL in 10 strains of mice [Johnson et al., 2000. Genomics 70, 171–180]. The present study was based on a conventional cross between two inbred strains, CB×B6.F 1 backcrossed to B6 with segregation for the putative +/ Ahl:Ahl/Ahl. These backcross progeny were exposed to 110 dB SPL noise for 8 h. All of the progeny were tested for auditory evoked brainstem responses and analyzed for any significant permanent threshold shift of NIHL. Cluster analyses were used to distinguish the two putative genotypes, the least affected with NIHL (+/ Ahl) and most affected with PTS ( Ahl/Ahl). Approximately 1/2 of the backcross progeny exhibited PTS, particularly at 16 kHz. These mice were genotyped for two D10Mit markers. Quantitative trait loci analyses (log of the odds=15) indicated association of the genetic factor within a few centiMorgan of the best evidence for Ahl [Johnson et al., 2000. Genomics 70, 171–180]. All of the available evidence supports a role for the Ahl gene in both AHL and NIHL among these strains of mice.