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

The C57BL/6J (B6) and DBA/2J (D2) inbred strains of mice exhibit an age-rel ated hearing loss (AHL) due to a recessive gene (Ahl) that maps to Chromoso me 10. The Ahl gene is also implicated in the susceptibility to noise-induc ed hearing loss (NIHL). The B6 mice (AhllAhl) are more susceptible to NIHL than the CBA/CaJ (CB) mice (+(Ahl)). The B6 x D2.F-1 hybrid mice (AhllAhl) are more susceptible to NIHL than the CB x B6.F-1 mice (+/Ahl) [Erway et al ., 1996. Hear. Res. 93, 181-187]. These genetic effects implicate the Ahl g ene as contributing to NIHL susceptibility. The present study demonstrates segregation for the putative Ahl gene and mapping of such a gene to Chromos ome 10, consistent with other independent mapping of. Ahl for AHL in 10 str ains of mice [Johnson et al., 2000. Genomics 70, 171-180]. The present stud y was based on a conventional cross between two inbred strains, CB x B6.F-1 backcrossed to B6 with segregation for the putative +/Ahl:AhllAhl. These b ackcross progeny were exposed to 110 dB SPL noise for 8 h. All of the proge ny 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 (AhllAhl). Approximately 1/2 of the backcr oss progeny exhibited PTS, particularly at 16 kHz. These mice were genotype d 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 ct 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. (C) 2001 Elsevier Science B.V. All r ights reserved.