STUDY ON THE MECHANISM OF DEAFNESS ASSOCIATED WITH MITOCHONDRIAL DNA ABNORMALITY

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(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