Qing Yin Zheng, Lihong Kui, Fuyi Xu, Tihua Zheng, Bo Li, Melinda McCarty, Zehua Sun, Aizheng Zhang, Luying Liu, Athena Starlard-Davenport, Ruben Stepanyan, Bo Hua Hu, Lu Lu
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引用次数: 5
摘要
近交系小鼠模型被广泛用于研究年龄相关性听力损失(AHL)。许多与AHL相关的基因已在各种菌株中被定位。然而，人们对具有相反功能的基因变体知之甚少，这些基因具有对听力损失的强大抵抗力。此前，我们报道了C57BL/6J (B6)和DBA/2J (D2)菌株在Cdh23中具有共同的听力损失等位基因。钙粘蛋白23 (Cdh23)基因是人类早发性听力损失的关键因素。在这项研究中，我们测试了由B6到D2杂交产生的54个BXD菌株的听力。54株中有5株甚至在2岁时仍保持正常阈值(20 dB SPL)，而在2岁时，两株亲本基本上都是聋子。进一步分析发现，16号染色体(Chr 16)上有一个年龄相关的听力保护(ahp)位点，位于57~76 Mb，最大LOD为5.7。少数2岁时听力良好的BXD菌株大致相当于90岁时听力良好的人的百分比。进一步研究确定ahp位点的候选基因和与年龄相关的AHL恢复力或抗性相关的分子机制是必要的。
An Age-Related Hearing Protection Locus on Chromosome 16 of BXD Strain Mice.
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.
期刊介绍：
Neural Plasticity is an international, interdisciplinary journal dedicated to the publication of articles related to all aspects of neural plasticity, with special emphasis on its functional significance as reflected in behavior and in psychopathology. Neural Plasticity publishes research and review articles from the entire range of relevant disciplines, including basic neuroscience, behavioral neuroscience, cognitive neuroscience, biological psychology, and biological psychiatry.
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