Program in Audiology and Communication Sciences, Washington University School of Medicine, St. Louis, MO 63110, United States.
Hear Res. 2010 Feb;260(1-2):47-53. doi: 10.1016/j.heares.2009.11.006. Epub 2009 Nov 12.
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.
我们最近在近交系小鼠中观察到单次噪声暴露的显著差异，其中 CBA/J 和 CBA/CaJ（CBA）小鼠的耳蜗内电位（EP）出现中度可逆性降低，而 C57BL/6J（B6）小鼠则没有（Ohlemiller，KK，Gagnon，PM，2007. 噪声损伤耳蜗细胞和结构的遗传依赖性。听觉研究 224，34-50）。CBA 中急性 EP 降低与螺旋韧带和血管纹的特征性病理学立即相关噪声后和 8 周后。B6xCBA F1 杂种鼠的分析表明，EP 降低及其解剖学相关性以常染色体显性方式共同遗传。进一步分析 N2 小鼠来自 F1 杂种回交到 B6 小鼠导致我们建议 EP 降低表型主要反映少数数量性状位点（QTLs）的影响。在这里，我们报告了使用来自（CBAxB6）xB6 回交的 106 只 N2 小鼠对 CBA/J 中 EP 降低表型进行 QTL 作图的结果。急性噪声后 EP 与分布在整个基因组中的 135 个标记物的相关性显示，18 号染色体上有一个单一的主要效应 QTL（12.5 cM，LOD 3.57）（Nirep，用于 EP QTL 的噪声诱导降低），以及 5 号和 16 号染色体上的两个边缘显著 QTL（LOD 1.43 和 1.73，分别）。我们的结果强调了一个事实，即不同的耳蜗结构可能通过非重叠基因的影响而具有对噪声的不同敏感性。虽然 Nirep 和类似作用的 QTL 似乎不会影响单次噪声暴露后的永久性听力损失程度，但它们可能会降低外侧壁在延长或持续暴露中的稳态“储备”，从而影响长期阈值稳定性。
