STUDY ON THE MECHANISM OF DEAFNESS ASSOCIATED WITH MITOCHONDRIAL DNA ABNORMALITY

(1)白化病豚鼠经口给予不同浓度（0.15%、0.5%和1%）的锗。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，并且在骨骼肌、内耳、心脏、肾脏或肝脏中没有显示出异常。用0.5%锗处理的大约三分之二的动物存活了两个月。这些动物的体重没有增加，骨骼肌明显萎缩。透射电镜观察发现，骨骼肌和肾脏的大量线粒体、心脏的部分线粒体和肝脏的少数线粒体变性并出现锗包涵体。ABR测量结果显示，在所有频率的中度阈值偏移。血管纹及其邻近区域的线粒体内可见大量锗包涵体和退行性改变。锗散在分布于椭圆囊和半规管的支持细胞、感觉上皮 ...更多信息 ALS和耳蜗和前庭神经纤维周围的区域，但这些组织表现出实际上正常的外观。这些结果表明，0.5%锗的管理引起的线粒体损伤的多个器官，包括耳蜗在豚鼠，这表明该实验模型是有用的，以研究耳蜗损伤线粒体脑肌病。阈值偏移可能主要是由于血管纹的损伤。(2)我们用斑点杂交法检测了1例母系遗传性糖尿病伴耳聋患者颞骨np3243的A → G点突变。在颞骨中，在整个耳蜗的血管纹和外毛细胞以及基底部的螺旋神经节细胞中观察到严重的变性。前庭和半规管内的内毛细胞和感觉上皮保存完好。(3)我们没有检测到顺式突变，在整个线粒体DNA中的3名患者谁窝藏A1555G点突变，并已开发氨基糖苷类药物引起的耳聋。在其中一人及其母亲的肌肉活检中发现了考克斯活性降低和线粒体包涵体，这表明这种突变本身可能会影响线粒体功能。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