Ohlemiller Kevin K
Department of Otolaryngology, Washington University, 660 S. Euclid, St. Louis, MO 63110, USA.
Brain Res. 2006 May 26;1091(1):89-102. doi: 10.1016/j.brainres.2006.03.017. Epub 2006 May 2.
Once an oddity, mice have become the most widely used hearing research model. Their value for research in noise-induced hearing loss (NIHL) stems from their high vulnerability to noise and reduced variance of results, made possible by genetic standardization. To research in age-related hearing loss (ARHL), they offer economies of small size and a short lifespan, both of which reduce housing costs. Inbred mouse strains show a wide range of noise sensitivities and rates of hearing loss with age. These can be studied using classical genetic analysis, as well as hypothesis-driven experiments utilizing genetic engineering. Through such investigations, presently 3 loci have been identified to date that contribute to NIHL, 10 that promote ARHL, and at least 6 loci that promote both. The types of genes involved implicate homeostatic and protective mechanisms as key to the appearance of either type of pathology and support a causal link between injury and some apparent ARHL. While the majority of mouse ARHL models examined most closely resemble sensory ARHL, recent work has identified mice possessing the essential characteristics of neural and strial ARHL. Using these models, it should be possible to identify genes and alleles that promote the major forms of ARHL and their combinations.
小鼠曾经是一种奇特的实验对象，如今已成为听力研究中使用最广泛的模型。它们在噪声性听力损失（NIHL）研究中的价值源于其对噪声的高度易感性以及结果方差的减小，这得益于基因标准化。在年龄相关性听力损失（ARHL）研究中，它们具有体型小和寿命短的优势，这两者都降低了饲养成本。近交系小鼠品系对噪声的敏感性和随年龄增长的听力损失率范围很广。这些可以通过经典遗传分析以及利用基因工程的假设驱动实验来研究。通过此类研究，目前已鉴定出3个与NIHL相关的基因座、10个促进ARHL的基因座以及至少6个同时促进这两种情况的基因座。所涉及的基因类型表明，稳态和保护机制是这两种病理类型出现的关键，并支持损伤与某些明显的ARHL之间存在因果联系。虽然大多数经过仔细研究的小鼠ARHL模型与感觉性ARHL最为相似，但最近的研究发现了具有神经性和血管纹性ARHL基本特征的小鼠。利用这些模型，应该有可能识别出促进ARHL主要形式及其组合的基因和等位基因。
