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

关联基因突变所致遗传性非综合征性耳聋发病机制分析

基本信息

批准号：
12470358
负责人：
KIKUCHI Toshihiko
金额：
$ 9.02万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470358/
关键词：
nonsyndromic deafness inner ear gap junction connexin voltage-gated potassium channel Kv3.1b Kv3.4 aquaporin non-syndromic deafness gas junction voltage-gated potassium channel Kv3.4 遺伝性難聴内リンパ電位免疫組織化学

项目摘要

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.

1) 连接蛋白 26 和连接 30 在哺乳动物耳蜗的上皮细胞和结缔组织细胞间隙连接系统中表达。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。 1 b 样免疫反应性存在于耳蜗侧壁的纤维细胞中。在齿间细胞和螺旋缘的纤维细胞以及角膜缘上暗细胞中也发现了免疫染色。 Kv3.4 样免疫反应性存在于螺旋韧带的纤维细胞和血管纹的基底细胞中。在柯蒂氏器中，在毛细胞和邻近的支持细胞中发现了类似 Kv3.4 的免疫反应性。根细胞和齿间细胞免疫染色呈阳性。3）在哺乳动物耳蜗中，部分结缔组织细胞和上皮细胞群中分别发现了水通道蛋白1和水通道蛋白4。4）长链醇与外淋巴融合导致耳蜗内电位（FP）下降。这些发现表明间隙连接通讯在哺乳动物耳蜗离子传输机制中的功能意义。5）在缺乏Brain-4的突变小鼠中，螺旋韧带II型纤维细胞和上区纤维细胞中Na,K-ATP酶样免疫反应性显着降低。连接蛋白 26 稀疏地分布在该突变小鼠耳蜗侧壁的纤维细胞中。这些发现表明，纤维细胞功能障碍和间隙连接跨细胞途径的中断可导致该突变小鼠耳蜗中EP的抑制，也表明间隙连接跨细胞途径在耳蜗中K+离子的转运中起着非常重要的作用。6）在遗传性病例中进行了详细的生理检查。非综合征性耳聋。