Analysis of the pathogenesis of the hereditary non syndromic deafness caused by mutations in connection genes

1)连接蛋白26和连接蛋白30在哺乳动物耳蜗上皮细胞和结缔组织细胞间隙连接系统中均有表达。相反，连接31定位于结缔组织细胞间隙连接系统。2)电压门控钾通道Kv3。耳蜗侧壁纤维细胞呈b样免疫反应性。牙间细胞、螺旋缘纤维细胞及唇上暗细胞均可见免疫染色。螺旋韧带纤维细胞和血管纹基底细胞存在kv3.4样免疫反应性。在Corti器官中，在毛细胞和邻近的支持细胞中发现了Kv3.4样免疫反应性。根细胞和牙间细胞免疫染色阳性。3)在哺乳动物耳蜗中，水通道蛋白1和水通道蛋白4分别存在于部分结缔组织细胞群和上皮细胞群中。4)淋巴管周围与长链醇的融合导致耳蜗电位（FP）下降。这些发现提示了间隙连接通讯在哺乳动物耳蜗离子传递机制中的功能意义。5)在缺乏Brain-4的突变小鼠中，螺旋韧带II型纤维细胞和胃上区纤维细胞的Na， k - atp样免疫反应性显著降低。连接蛋白26在突变小鼠耳蜗侧壁的纤维细胞中稀疏分布。这些发现表明，纤维细胞功能障碍和通过间隙连接的跨细胞途径中断可导致该突变小鼠耳蜗EP下降，也表明通过间隙连接的跨细胞途径在耳蜗K+离子的运输中起着非常重要的作用。6)对遗传性非综合征性耳聋进行详细的生理检查。

1) Connexin 26 and connection 30 were expressed in both epithelial cell and connective tissue cell gap junction systems in the mammalian cochlea. In contrast, connection 31 was localized to the connective tissue cell gap junction system.2) Voltage-gated potassium channel Kv3. 1 b-like immunoreactivity was present in the fibrocytes of the cochlear lateral wall. Immunostaining was also found in the interdental cells and the fibrocytes of the spiral limbus and in the supralimbal dark cells. Kv3.4-like immunoreactivity was present in the fibrocytes of the spiral ligament and the basal cells of the stria vascularis. In the organ of Corti, Kv3.4- like immunoreactivity was found in the hair cells and the neighboring supporting cells. The root cells and interdental cells were positively immunostained.3) In the mammalian cochlea, aquaporin-1 and aquaporin-4 were found in some populations of the connective tissue cells and epithelial cells respectively.4) The perilymphatlc per fusion with the long chain alcohol caused the depression of the endocochlear potential (FP). These findings suggested the functional significance of the gap junctional communication in the ion transporting mechanism in the mammalian cochlea.5) In the mutant mouse lacking Brain-4, Na,K-ATPase-like immunoreactivity in the type II fibrocytes of the spiral ligament and the fibrocytes in the suprastrial zone was remarkably decreased. Connexin 26 was sparsely distributed among these fibrocytes in the cochlear lateral wall of this mutant mouse. These findings suggest that a dysfunction of fibrocytes and an interruption of the transcellular route via gap junctions can cause a depression of EP in the cochlea of this mutant mouse, and also suggest that the transcellular pathway via gap junctions plays a very important role in the transport of K+ ions in the cochlea.6) Detailed physiological examinations were carried out in the cases of hereditary nonsyndromic deafness.