The effect of an age-related hearing loss gene (Ahl) on noise-induced hearing loss and cochlear damage from low-frequency noise.
Inbred C57BL/6J mice carry two copies of an age-related hearing loss gene (Ahl). It has been shown that these mice begin losing high-frequency hearing at two months. Several functional studies have reported that the Ahl gene renders mice more susceptible to noise-induced hearing loss (NIHL) than strains which do not carry this gene [e.g., Hear. Res. 93 (1996) 181; Hear. Res. 155 (2001) 82; J. Assoc. Res. Otolaryngol. 2 (2001) 233]. Johnson et al. [Hear. Res. 114 (1997) 83] developed a congenic B6.CAST-+Ahl mouse which carries the wild-type allele from Mus musculus castaneus at the Ahl locus. Five each of young C57BL/6J males and females, and B6.CAST-+Ahl males were exposed to a 4-kHz octave band of noise at 108 dB SPL for 4 h. Non-noise-exposed mice of the same strains and age served as controls. The noise-exposed mice were functionally tested for ABR thresholds and DPOAE levels pre-exposure and three times post-exposure: 0 days to determine the magnitude of temporary threshold shift (TTS); 6 days to determine rate of recovery; and 20 days to determine the magnitude of permanent threshold shift (PTS). At 20 days post-exposure, the animals underwent cardiac perfusion to fix their cochleae. The isolated cochleae were embedded in plastic and dissected into flat preparations. By phase-contrast microscopy, each cochlea was evaluated from apex to base to quantify the losses of hair cells, nerve fibers and stria vascularis and to localize stereocilia damage. Functional data from each mouse were aligned with the cytocochleogram using the frequency-place map of Ou et al. [Hear. Res. 145 (2000) 111; Hear. Res. 145 (2000) 123]. Sizable variation in the magnitude of TTS, PTS and hair-cell loss was found among mice of the same genetic strain. The congenic B6.CAST-+Ahl male mice had significantly less TTS immediately post-exposure than C57BL/6J males or females but not less PTS or hair-cell losses at 20 days post-exposure. These results indicate that, at one month of age, mice carrying two copies of the Ahl gene have an increased susceptibility to TTS from a low-frequency noise before they have any indication of age-related hearing or hair-cell loss. However, this appeared not to be the case for PTS. The Ahl gene appears to play a role in susceptibility to NIHL but, other genes as well as systemic and local factors must also be involved.
Harding
Gary W
GW
Department of Otolaryngology, Box 8115, Washington University School of Medicine, St. Louis, MO 63110, USA. hardingg@wustl.edu
Bohne
Barbara A
BA
Vos
Jeremy D
JD
D000818:Animals; D001300:Audiometry, Evoked Response; D001305:Auditory Fatigue; D001309:Auditory Threshold; D003051:Cochlea / Q000473:pathology / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006317:Hearing Loss, Noise-Induced / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009622:Noise / Q000009:adverse effects*; D017084:Otoacoustic Emissions, Spontaneous; D011304:Presbycusis / Q000235:genetics*