Leibovici Michel, Safieddine Saaid, Petit Christine
Institut Pasteur, Unite de Genetique et Physiologie de l'Audition, Paris, France.
Curr Top Dev Biol. 2008;84:385-429. doi: 10.1016/S0070-2153(08)00608-X.
Hearing impairment is a frequent condition in humans. Identification of the causative genes for the early onset forms of isolated deafness began 15 years ago and has been very fruitful. To date, approximately 50 causative genes have been identified. Yet, limited information regarding the underlying pathogenic mechanisms can be derived from hearing tests in deaf patients. This chapter describes the success of mouse models in the elucidation of some pathophysiological processes in the auditory sensory organ, the cochlea. These models have revealed a variety of defective structures and functions at the origin of deafness genetic forms. This is illustrated by three different examples: (1) the DFNB9 deafness form, a synaptopathy of the cochlear sensory cells where otoferlin is defective; (2) the Usher syndrome, in which deafness is related to abnormal development of the hair bundle, the mechanoreceptive structure of the sensory cells to sound; (3) the DFNB1 deafness form, which is the most common form of inherited deafness in Caucasian populations, mainly caused by connexin-26 defects that alter gap junction communication between nonsensory cochlear cells.
听力障碍在人类中是一种常见病症。对早发性孤立性耳聋致病基因的鉴定始于15年前，成果丰硕。迄今为止，已鉴定出约50个致病基因。然而，从耳聋患者的听力测试中获得的关于潜在致病机制的信息有限。本章描述了小鼠模型在阐明听觉感觉器官——耳蜗的一些病理生理过程方面的成功。这些模型揭示了耳聋遗传形式起源处的各种结构和功能缺陷。以下三个不同例子说明了这一点：（1）DFNB9型耳聋，一种耳蜗感觉细胞的突触病变，其中 otoferlin 存在缺陷；（2）Usher 综合征，其中耳聋与毛束异常发育有关，毛束是感觉细胞对声音的机械感受结构；（3）DFNB1型耳聋，这是白种人群中最常见的遗传性耳聋形式，主要由连接蛋白-26缺陷引起，该缺陷改变了耳蜗非感觉细胞之间的缝隙连接通讯。
