前期研究发现Connexin26基因敲除小鼠耳蜗发育过程中内淋巴电位形成障碍，其具体机制并不清楚。分泌型MicroRNAs是细胞间新型通讯途径和信息载体，近期我们发现分泌型MicroRNAs在不同缝隙连接间横向传递存在差异，本课题拟应用诱导性Connexin26基因敲除小鼠模型，研究耳蜗发育过程中通过缝隙连接系统构成的血管纹中间细胞-基底细胞-纤维细胞合胞体中miR-205横向传递障碍对内淋巴电位形成的影响，探讨miR-205通过调控内向整流钾离子通道KCNJ10导致内淋巴电位形成障碍的机制，同时体内外双靶向逆转miR-205通讯异常联合发育早期恢复Connexin26表达，以期实现在重建内淋巴电位基础上挽救Connexin26通道功能。为Connexin26缺陷导致非综合性遗传性耳聋提供新的机制和治疗思路。

Our previous research revealed that endocochlear potential(EP) dyspoiesis during key developmental stage in GJB2 mutation mice model，however，the mechanism is still obscure. Secretory miRNAs orchestrate a broad range of intercellular communication events. Our recent data demonstrated a different miRNAs transduction pattern among gap junctions. In this study, we propose to investigate the mechanism of miR-205 horizontal communication disorder mediated EP dyspoiesis in the intermediate cells - basal cells - fibrocytes syncytium connected by connexins during cochlea development，as well as the role of miR-205 mediated inwardly rectifying potassium channels KCNJ10 in the EP generation. We will also explore the potential way to reverse the miR-205 communication disorder and to recover the expression of Cx26 in the early developmental stage. Our ultimate goal is to double target for rebuilding the EP and to rescue the channel function of Cx26. This study may provide novel targets on the therapeutic interventions of nonsyndromic inherited deafness caused by Cx26 deficiency.