GJB2基因p.V37I突变是导致我国汉族人群听力障碍的重要遗传易感性突变，该突变所致听力表型差异极大，其致病机制尚不明确，推测免疫应答极有可能是致病的关键因素。我们前期构建了Gjb2基因p.V37I突变敲入小鼠并发现介导免疫反应的Fcer1g基因在其耳蜗内存在特异性高表达。基于已有研究：FCER1G基因可通过免疫级联反应影响细胞内外Ca2+平衡，我们提出科学假设：FCER1G基因通过改变内耳微环境中Ca2+平衡从而进一步破坏p.V37I突变蛋白的离子通透性，是调控GJB2基因p.V37I突变听力表型的关键分子。本研究拟从分子、细胞、组织、模式动物和临床病例等多层次阐明FCER1G基因调控GJB2基因p.V37I突变听力表型的分子机制，并利用阻断免疫相关信号通路的拮抗剂进行干预。本项目将从免疫应答这个新角度探讨GJB2基因p.V37I突变的致病机制，为耳聋的防治提供新思路。

P.V37I variant of GJB2 gene is one of the most important genetic susceptibility mutation responsible for hearing loss in Chinese Hans. Clinically, phenotype of hearing loss of p.V37I exclusive mutation cases presented great difference. However, the pathogenic mechanism remains unknown, and it is probably associated with immunological factors. We established previously Gjb2-V37I/V37I mice model and certified its specific overexpression of Fcer1g gene, which mediates immunologic reation in cochlear. Based on previous study, FCER1G gene influences intra-or extra-cellular Ca2+ ions equilibrium by immune response. Thus, we hypothesized that FCER1G is key molecular resulting in difference phenotype of p.V37I mutation of GJB2 gene by immunological signaling pathways related to disequilibrium of Ca2+ in the cochlear and ionic permeability of p.V37I mutant protein . This study will further explore regulation effect of FCER1G gene on p.V37I variant of GJB2 and its mechanism by levels of molecule, cell, tissue, animal models and clinical cases, and interve by antagonist of immunological pathways as well, in order to provide new thinking for prevention and therapy on hearing loss.