White Cory H, Ohmen Jeffrey D, Sheth Sonal, Zebboudj Amina F, McHugh Richard K, Hoffman Larry F, Lusis Aldons J, Davis Richard C, Friedman Rick A
Department of Cell Biology and Genetics, House Ear Institute, Gonda Center for Cellular and Molecular Biology, 2100 West 3rd Street, Los Angeles, CA 90057, USA.
Mamm Genome. 2009 Apr;20(4):207-13. doi: 10.1007/s00335-009-9178-5. Epub 2009 Apr 1.
Noise-induced hearing loss (NIHL) is one of the more common sources of environmentally induced hearing loss in adults. In a mouse model, Castaneous (CAST/Ei) is an inbred strain that is resistant to NIHL, while the C57BL/6J strain is susceptible. We have used the genome-tagged mice (GTM) library of congenic strains, carrying defined segments of the CAST/Ei genome introgressed onto the C57BL/6J background, to search for loci modifying the noise-induced damage seen in the C57BL/6J strain. NIHL was induced by exposing 6-8-week old mice to 108 dB SPL intensity noise. We tested the hearing of each mouse strain up to 23 days after noise exposure using auditory brainstem response (ABR). This study identifies a number of genetic loci that modify the initial response to damaging noise, as well as long-term recovery. The data suggest that multiple alleles within the CAST/Ei genome modify the pathogenesis of NIHL and that screening congenic libraries for loci that underlie traits of interest can be easily carried out in a high-throughput fashion.
噪声性听力损失（NIHL）是成人环境性听力损失中较常见的原因之一。在小鼠模型中，Castaneous（CAST/Ei）是一种对NIHL具有抗性的近交系，而C57BL/6J品系则易感。我们利用携带导入到C57BL/6J背景上的CAST/Ei基因组特定片段的同源基因系基因组标记小鼠（GTM）文库，来寻找修饰C57BL/6J品系中噪声诱导损伤的基因座。通过将6-8周龄小鼠暴露于108 dB SPL强度的噪声中来诱导NIHL。我们在噪声暴露后长达23天使用听觉脑干反应（ABR）测试了每个小鼠品系的听力。本研究确定了一些修饰对损伤性噪声的初始反应以及长期恢复的基因座。数据表明，CAST/Ei基因组内的多个等位基因修饰了NIHL的发病机制，并且以高通量方式很容易对同源基因文库进行感兴趣性状潜在基因座的筛选。
