| Project/Area Number |
04557012
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Instute of Gerontology, Nippon Mrdical School (1994)
Jichi Medical University (1992-1993) |
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Principal Investigator |
OHTA Shigeo Division of Biochemistry, Institute of Gerontology, Nippon Medical School, Professor, 老人病研究所, 教授 (00125832)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Jun-icji Institute of Biological Sciences, University of Tsukuba, Associate Professor, 生物科学系, 助教授 (60142113)
香川 靖雄 自治医科大学, 医学部, 教授 (30048962)
猪原 直弘 自治医科大学, 医学部, 助手 (60232576)
遠藤 仁司 自治医科大学, 医学部, 助手 (50221817)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥18,500,000 (Direct Cost: ¥18,500,000)
Fiscal Year 1994: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1993: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1992: ¥12,700,000 (Direct Cost: ¥12,700,000)
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| Keywords | Mitochondria / Transgenic mouse / Cybrid / Respiratory chain / particle gun / Cell fusion / Mitochondrial encephalomyopathy / Cardiomyopathy / タンパク質合成 / Alpers病 / 老化 / パーラィクルガン / ミトコンドリアDNA / ミトコンドリア胸筋症 / 遺伝子病 / 遺伝子導入 / 金属粒子 / 遺伝子銃 |
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| Research Abstract |
mtDNA with a point mutation in the tRNA^<Ile> gene at nucleotide position 4269 found in a patient with fatal cardiomyopathy and mtDNA with a point mutation in the tRNA^<Arg> gene at 10410 found in a patient with Alpers disease were transferred cytoplasmically to rhoﾟ HeLa cells (HeLa cells lacking mtDNA) to determine whether these novel mtDNA mutations in the tRNA genes are responsible for the defects in mitochondrial respiration function observed in these diseases. Cybrid clones (clones of rhoﾟ HeLa cells with mtDNA from the patients) were isolated, and respiratory function and morphology of the mitochondria of the cybrid clones containing wild-type mtDNA and mutant mtDNA predominantly were compared. The results showed that accumulation of mutant mtDNA at 4269 alone without defects in the nuclear genome was sufficient to produce a disease phenotype, while mutant mtDNA at 10410 was not related to pathogenesis and reflected one of the rare polymorphic sites of human mtDNA.Moreover, we found that mitochondria in living cells were significantly swollen only when they contained predominantly the pathogenic mutant mtDNA,suggesting that the functional abnormalitiy of mitochondria induced by pathogenic mtDNA mutations in tRNA genes is always associated with their swollen structure.
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