Inbred mouse models are widely used to study age-related hearing loss (AHL). Many genes associated with AHL have been mapped in a variety of strains. However, little is known about gene variants that have the converse function—protective genes that confer strong resistance to hearing loss. Previously, we reported that C57BL/6J (B6) and DBA/2J (D2) strains share a common hearing loss allele in Cdh23. The cadherin 23 (Cdh23) gene is a key contributor to early-onset hearing loss in humans. In this study, we tested hearing across a large family of 54 BXD strains generated from B6 to D2 crosses. Five of 54 strains maintain the normal threshold (20 dB SPL) even at 2 years old—an age at which both parental strains are essentially deaf. Further analyses revealed an age-related hearing protection (ahp) locus on chromosome 16 (Chr 16) at 57~76 Mb with a maximum LOD of 5.7. A small number of BXD strains at 2 years with good hearing correspond roughly to the percentage of humans who have good hearing at 90 years old. Further studies to define candidate genes in the ahp locus and related molecular mechanisms involved in age-related resilience or resistance to AHL are warranted.

中文翻译：

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BXD 品系小鼠 16 号染色体上与年龄相关的听力保护位点。

近交系小鼠模型广泛用于研究与年龄相关的听力损失 (AHL)。许多与 AHL 相关的基因已在多种菌株中被定位。然而，人们对具有相反功能的基因变异知之甚少——保护性基因对听力损失具有很强的抵抗力。以前，我们报道过 C57BL/6J (B6) 和 DBA/2J (D2) 菌株在Cdh23中有一个共同的听力损失等位基因。钙粘蛋白 23 ( Cdh23) 基因是导致人类早发性听力损失的关键因素。在这项研究中，我们测试了从 B6 到 D2 杂交产生的 54 个 BXD 菌株大家族的听力。54 种菌株中有 5 种即使在 2 岁时也能保持正常阈值 (20 dB SPL)——在这个年龄，父母的两种菌株基本上都是聋子。进一步的分析揭示了16 号染色体 (Chr 16) 上与年龄相关的听力保护 ( ahp ) 基因座 57~76 Mb，最大 LOD 为 5.7。2 岁时具有良好听力的少量 BXD 菌株大致对应于 90 岁时具有良好听力的人的百分比。有必要进一步研究以确定ahp基因座中的候选基因以及涉及与年龄相关的恢复力或对 AHL 的抵抗力的相关分子机制。