Genetic dependence of cochlear cells and structures injured by noise.
The acute and permanent effects of a single damaging noise exposure were compared in CBA/J, C57BL/6 (B6), and closely related strains of mice. Two hours of broadband noise (4-45 kHz) at 110 dB SPL led to temporary reduction in the endocochlear potential (EP) of CBA/J and CBA/CaJ (CBA) mice and acute cellular changes in cochlear stria vascularis and spiral ligament. For the same exposure, B6 mice showed no EP reduction and little of the pathology seen in CBA. Eight weeks after exposure, all mice showed a normal EP, but only CBA mice showed injury and cell loss in cochlear lateral wall, despite the fact that B6 sustained larger permanent threshold shifts. Examination of noise injury in B6 congenics carrying alternate alleles of genes encoding otocadherin (Cdh23), agouti protein, and tyrosinase (albinism) indicated that none of these loci can account for the strain differences observed. Examination of CBA x B6 F1 mice and N2 backcross mice to B6 further indicated that susceptibility to noise-related EP reduction and associated cell pathology are inherited in an autosomal dominant manner, and are established by one or a few large effect quantitative trait loci. Findings support a common genetic basis for an entire constellation of noise-related cochlear pathologies in cochlear lateral wall and spiral limbus. Even within species, cellular targets of acute and permanent cochlear noise injury may vary with genetic makeup.
Ohlemiller
Kevin K
KK
Department of Otolaryngology, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, United States. kohlemiller@wustl.edu
Gagnon
Patricia M
PM
D000200:Action Potentials; D000818:Animals; D001309:Auditory Threshold; D003051:Cochlea / Q000473:pathology* / Q000503:physiopathology; D003433:Crosses, Genetic; D005072:Evoked Potentials, Auditory; D006317:Hearing Loss, Noise-Induced / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D008543:Melanins / Q000235:genetics; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D013045:Species Specificity
D008543:Melanins