STUDY ON THE MECHANISM OF DEAFNESS ASSOCIATED WITH MITOCHONDRIAL DNA ABNORMALITY

(1)给白化豚鼠灌胃不同浓度的锗(0.15%、0.5%、1%)。用1%锗处理的动物在几周内死亡。用0.15%锗处理的动物直到6个月才死亡，骨骼肌、内耳、心脏、肾脏或肝脏没有表现出异常。用0.5%的锗处理的大约三分之二的动物存活了两个月。这些动物没有增加体重，它们的骨骼肌明显萎缩。透射电子显微镜观察发现，骨骼肌和肾脏中有大量线粒体变性和锗包涵体，心脏中有部分线粒体，肝脏中有少量线粒体。ABR测量显示，在所有频率上都有适度的阈值漂移。血管纹及其邻近区域线粒体内可见大量锗包涵体和变性改变。Ge也散在分布于支持细胞中，椭圆形和半圆形中的感觉上皮可以…肌萎缩侧索硬化症较多，耳蜗神经纤维和前庭神经纤维周围区域较多，但这些组织外观基本正常。这些结果表明，0.5%锗可引起豚鼠包括耳蜗在内的多个器官的线粒体损伤，提示该实验模型可用于研究线粒体脑肌病的耳蜗性损伤。阈值偏移可能主要是由于我的血管纹受损所致。(2)应用斑点杂交技术从一例母系遗传性糖尿病和耳聋患者的颞骨组织中检测到A-G点突变。在这个颞骨中，血管纹和外毛细胞严重变性，遍及耳蜗底和底部的螺旋神经节细胞。相比之下，前庭和半规管的内毛细胞和感觉上皮保存完好。(3)在3例携带A1555G点突变并发生氨基糖苷类致聋的患者中，未检测到线粒体DNA的顺式突变。在其中一人和他的母亲身上，在肌肉活检组织中发现了COX活性降低和线粒体包涵体，这表明这种突变本身可能影响线粒体功能。较少

(1) Albino guinea pigs were orally given germanium at different concentrations (0.15%, 0.5%, and 1%). Animals treated with 1% germanium died within a few weeks. Animals treated with 0.15% germanium did not die until 6 months and showed no abnormalities in the skeletal muscle, inner ear, heart, kidney or liver. Approximately two-thirds animals treated with 0.5 % germanium survived for two months. These animals did not gain body weight, and their skeletal muscles were apparently atrophic. TEM observation revealed degeneration and germanium inclusion in a lot of mitochondria in the skeletal muscle and kidney, some mitochondria in the heart, and a few mitochondria in the liver. ABR measurements revealed moderate threshold shifts at all frequencies. A lot of germanium inclusion and degenerative changes were found in the mitochondria in the stria vascularis and its adjacent areas. Germanium was also scattered in the supporting cells, the sensory epithelium in the utricle and semicircular can … More als, and areas around the cochlear and vestibular nerve fibers, but these tissues showed virtually normal appearance. These findings indicate that 0.5% germanium administration induces mitochondrial damages in multiple organs including the cochlea in the guinea pigs, suggesting that this experimental model is useful to investigate cochlear damage in mitochondrial encephalomyopathy. The threshold shifts may be due chiefly to damage to me stria vascularis. (2) We detected an A-to-G point mutation at np 3243 from temporal bone of a patient with maternally inherited diabetes and deafness using dot-blotting method. In this temporal bone, severe degeneration was observed in the stria vascularis and outer hair cells throughout the cochlea and spiral ganglion cells in the base. In contrast, the inner hair cells and sensory epithelium in the vestibulum and semicircular canals were well preserved. (3) We did not detect cis-mutations in the whole mitochondrial DNAs in three patients who harbored an A1555G point mutation and had developed aminoglycoside-induced deafness. In one of them and his mother, reduced COX activities and mitochondrial inclusion bodies were found in muscle biopsies, suggesting that this mutation itself may affect mitochondrial function. Less