前期研究发现耳蜗发育早期Pillar细胞中微管乙酰化异常是GJB2基因（编码Connexin26蛋白，Cx26）缺失突变小鼠耳蜗Corti器隧道不能开放的分子基础，但其机制并不清楚。通过在耳蜗听觉上皮特异性cDNA文库中筛选Cx26相互作用蛋白及Co-IP验证，我们发现高尔基体结构蛋白乙酰辅酶A结合域蛋白3（ACBD3）与Cx26存在相互作用。本课题拟应用GJB2基因敲除小鼠及构建的GJB2突变细胞模型，探索Cx26通过与高尔基体结构蛋白ACBD3作用调控微管蛋白乙酰化酶ATAT1介导的微管蛋白α-Tublin第40位氨基酸乙酰化的机制，并通过腺相关病毒2/1发育早期经耳蜗中阶转染GJB2基因敲除小鼠促进发育关键时期微管正常形成，以期在重建Corti器隧道结构的基础上恢复Corti器功能，为Cx26缺陷导致非综合征遗传性耳聋提供基于机制的治疗靶点和思路。

Our previous data revealed that microtube acetylation dysfunction in Pillar cell during cochlear early developmental stage was the key molecular point of Cochlear tunnel remained close in GJB2 gene (encoded Connexin26, Cx26) mutation mice, however, the mechanism is still obscure. By screening an auditory epithelium-specific cDNA library and Co-IP, our recent data demonstrated that Acyl-coenzyme A binding domain containing protein3 (ACBD3) interactive with Cx26. In this grant we propose to explore the mechanism that Cx26 interaction with ACBD3 regulate tubulin acetyltransferase ATAT1 mediated α-tubulin Lys-40 acetylation dysfunction by using GJB2 gene mutation mouse model and cell lines. We will also use AAV2/1 virus at the early postnatal stage to inoculate ATAT1 and Cx26 into the cochlea scala media in GJB2 gene mutation mice, our ultimate goal is to double target for reconstruction the structure of cochlear tunnel and to restore Cochlear function. This study may provide novel targets based on mechanism for the therapeutic interventions and strategies of nonsyndromic inherited deafness caused by GJB2 gene mutation.