BXD 品系小鼠 16 号染色体上与年龄相关的听力保护基因座

An Age-Related Hearing Protection Locus on Chromosome 16 of BXD Strain Mice.

机构信息

Department of Otolaryngology-Head and Neck Surgery, Case Western Reserve University, Cleveland, Ohio, USA.

Hearing and Speech Rehabilitation Institute, College of Special Education, Binzhou Medical University, Yantai, China.

出版信息

Neural Plast. 2020 Jun 8;2020:8889264. doi: 10.1155/2020/8889264. eCollection 2020.

DOI:10.1155/2020/8889264

PMID:32587610

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7298343/

Abstract

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 . The cadherin 23 () 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 () 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 locus and related molecular mechanisms involved in age-related resilience or resistance to AHL are warranted.

摘要

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品系中定位。然而，对于具有相反功能的基因变体（即赋予对听力损失强抗性的保护性基因）知之甚少。此前，我们报道 C57BL/6J（B6）和 DBA/2J（D2）品系在. 基因中共享一个常见的听力损失等位基因。钙黏蛋白 23（）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，我们对来自 B6 到 D2 杂交的 54 个 BXD 近交系大家族进行了听力测试。在 2 岁时，有 5/54 个品系保持正常阈值（20 dB SPL）-此时两个亲本品系基本失聪。进一步的分析显示，16 号染色体（Chr 16）上存在一个与年龄相关的听力保护（）位点，位于 57~76 Mb 之间，最大 LOD 为 5.7。少数在 2 岁时听力良好的 BXD 品系大致对应于 90 岁时听力良好的人类比例。进一步研究该位点的候选基因以及涉及年龄相关弹性或对 AHL 抗性的相关分子机制是必要的。