A major effect QTL on chromosome 18 for noise injury to the mouse cochlear lateral wall.

We recently demonstrated a striking difference among inbred mouse strains in the effects of a single noise exposure, whereby CBA/J and CBA/CaJ (CBA) mice show moderate reversible reduction in the endocochlear potential (EP) while C57BL/6J (B6) mice do not (Ohlemiller, K.K., Gagnon, P.M., 2007. Genetic dependence of cochlear cells and structures injured by noise. Hear. Res. 224, 34-50). Acute EP reduction in CBA was reliably associated with characteristic pathology of the spiral ligament and stria vascularis, both immediately after noise and 8weeks later. Analysis of B6xCBA F1 hybrid mice indicated that EP reduction and its anatomic correlates are co-inherited in an autosomal dominant manner. Further analysis of N2 mice resulting from the backcross of F1 hybrids to B6 mice led us to suggest that the EP reduction phenotype principally reflects the influence of a small number of quantitative trait loci (QTLs). Here we report the results of QTL mapping of the EP reduction phenotype in CBA/J using 106 N2 mice from a (CBAxB6)xB6 backcross. Correlation of acute post-noise EP with 135 markers distributed throughout the genome revealed a single major effect QTL on chromosome 18 (12.5 cM, LOD 3.57) (Nirep, for noise-induced reduction in EP QTL), and two marginally significant QTLs on chromosomes 5 and 16 (LOD 1.43 and 1.73, respectively). Our results underscore that fact that different cochlear structures may possess different susceptibilities to noise through the influence of non-overlapping genes. While Nirep and similar-acting QTLs do not appear to influence the extent of permanent hearing loss from a single noise exposure, they could reduce the homeostatic 'reserve' of the lateral wall in protracted or continual exposures, and thereby influence long term threshold stability. Copyright 2009 Elsevier B.V. All rights reserved.