Tmem30b在小鼠内耳发育和听觉功能中的作用及其机制研究

内耳发育异常和毛细胞的不可逆损伤是导致感音神经性耳聋的重要原因。申请人前期在国自然青年基金资助下，通过RNA-seq系统地比较Lgr5阳性内耳干细胞与Lgr5阴性支持细胞的转录组学差异，发现细胞周期基因Tmem30b很有可能在调控内耳发育和再生过程中发挥了重要作用。我们的预实验结果发现Tmem30b在小鼠耳蜗中高表达，并且Tmem30b敲除小鼠出现毛细胞缺失和听力下降，但Tmem30b在内耳发育和听功能中的具体作用及其机制尚不清楚。本项目将系统地研究Tmem30b在内耳发育和听功能中的作用及其机制，拟实现目标：一研究不同时间点Tmem30b在内耳中的表达；二通过Tmem30b敲除小鼠研究Tmem30b对内耳胚胎发育期的影响；三通过Tmem30b敲除小鼠研究Tmem30b对出生后小鼠听觉功能发育的影响；四探究Tmem30b缺失致聋的分子机制，从而为临床上诊治感音神经性耳聋提供理论和实验依据。

Inner ear dysplasia and irreversible damage of hair cells are the important causes of sensorineural hearing loss. We have previously compared the transcriptomics of Lgr5 positive inner ear stem cells and Lgr5 negative support cells by RNA-seq with the support of the National Science Foundation for Young Scientists, and found that the cell cycle-related gene Tmem30b might be a key gene which could regulate the development and regeneration of inner ear. Our pre-experimental results found that Tmem30b is highly expressed in mouse cochlea, and Tmem30b knockout mice have hair cell loss and hearing loss, but the role of Tmem30b in inner ear development and hearing function and its specific mechanism are still not clear. This project will systematically study the role of Tmem30b in the inner ear development and auditory function, and the following goals are going to be achieved.The first one is to study the expression of Tmem30b in the inner ear at different time points; The second one is to study the effect Tmem30b played in the development of embryo period of the inner ear through Tmem30b knockout mice; The third one is to study the effects of Tmem30b played in the postnatal development of auditory function through knockout mice; And the last one is to explore the molecular mechanism of Tmem30b, so as to provide theoretical and experimental basis for clinical diagnosis and treatment of sensorineural deafness.