Friedman Lilach M, Dror Amiel A, Avraham Karen B
Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Int J Dev Biol. 2007;51(6-7):609-31. doi: 10.1387/ijdb.072365lf.
Hereditary sensorineural hearing loss, derived from inner ear defects, is the most common hereditary disability with a prevalence of 1 in 1,000 children, although it can be present in up to 15% of births in isolated communities. The mouse serves as an ideal animal model to identify new deafness-related genes and to study their roles in vivo. This review describes mouse models for genes that have been linked with hearing impairment (HI) in humans. Mutations in several groups of genes have been linked with HI in both mice and humans. Mutant mice have been instrumental in elucidating the function and mechanisms of the inner ear. For example, the roles of collagens and tectorins in the tectorial membrane, as well as the necessity of intact links between the hair cell projections, stereocilia and kinocilia, have been discovered in mice. Accurate endolymph composition and the proteins which participate in its production were found to be crucial for inner ear function, as well as several motor proteins such as prestin and myosins. Two systematic projects, KOMP and EUCOMM, which are currently being carried out to create knock-out and conditional mutants for every gene in the mouse genome, promise that many additional deafness-related genes will be identified in the next years, providing models for all forms of human deafness.
遗传性感音神经性听力损失源于内耳缺陷,是最常见的遗传性残疾,在每1000名儿童中的患病率为1例,不过在一些与世隔绝的社区中,其在出生人口中的占比可达15%。小鼠是鉴定新的耳聋相关基因并在体内研究其作用的理想动物模型。本综述描述了与人类听力障碍(HI)相关基因的小鼠模型。几组基因的突变在小鼠和人类中均与HI有关。突变小鼠有助于阐明内耳的功能和机制。例如,在小鼠中发现了胶原蛋白和盖膜蛋白在盖膜中的作用,以及毛细胞突起、静纤毛和动纤毛之间完整连接的必要性。还发现精确的内淋巴成分及其产生过程中涉及的蛋白质对于内耳功能至关重要,还有一些运动蛋白如 prestin 和肌球蛋白也是如此。目前正在开展的两个系统性项目,即小鼠基因敲除计划(KOMP)和欧洲条件性小鼠突变体计划(EUCOMM),旨在为小鼠基因组中的每个基因创建基因敲除和条件性突变体,有望在未来几年鉴定出更多与耳聋相关的基因,为所有形式的人类耳聋提供模型。