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缝隙连接系统中均有表达。相反，连接31定位于结缔组织细胞缝隙连接系统2)电压门控钾通道Kv3。1耳蜗侧壁成纤维细胞呈b样免疫反应。牙间细胞、螺旋缘成纤维细胞及缘上暗细胞也有免疫染色。Kv3.4免疫反应阳性细胞位于螺旋韧带的纤维细胞和血管纹的基底细胞。在Corti器官中，毛细胞及邻近的支持细胞呈Kv3.4样免疫反应。3)在哺乳动物耳蜗内，水通道蛋白-1和水通道蛋白-4分别存在于结缔组织细胞和上皮细胞的某些群体中。4)外淋巴管与长链酒精的融合导致耳蜗内电位(FP)的降低。这些结果提示缝隙连接通讯在哺乳动物耳蜗离子转运机制中的功能意义。5)在缺乏脑-4，Na，K-ATPase样免疫反应的突变小鼠中，螺旋韧带的II型纤维细胞和工业上带的纤维细胞的免疫反应明显减少。在该突变小鼠的耳蜗侧壁上，缝隙连接蛋白26在这些纤维细胞中分布稀疏。这些发现表明，纤维细胞功能障碍和通过缝隙连接的跨细胞途径中断可以导致该突变小鼠耳蜗内EP的抑制，也表明通过缝隙连接的跨细胞途径在耳蜗钾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患者进行了详细的生理检查。

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.