1994 Fiscal Year Final Research Report Summary
Construction of transgenic mice into which mutant mitochondrial DNA is artificially introduced.
| 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)
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| Project Period (FY) |
1992 – 1994
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| Keywords | Mitochondria / Transgenic mouse / Cybrid / Respiratory chain / particle gun / Cell fusion / Mitochondrial encephalomyopathy / Cardiomyopathy |
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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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[Publications] Hayashi, J-I., Ohta, S.Takai, D., Miyabayashi, S., Sakuta, R., Goto, Y-i., and Nonaka, I.: "Accumulation of mtDNA with a mutation at position 3271 in tRNA-Leu (UUR) gene introduced from a MELAS patient to HeLa cells lacking mtDNA results in progressive inhibition of mitochondrial respiratory function." Biochem.Biophys.Res.Commun.197 (3). 1049-1055 (1993)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Shiraiwa, N., Ishii, A., Iwamoto, H., Mizusawa, H., Kagawa, Y., and Ohta, S.: "Content of mutant mitochondrial DNA and organ-dysfunction in a patient with a MELAS-subgroup of mitochondrial encephalomyopathies." J.Neurol.Sci.120. 174-179 (1993)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Hayashi, J-I., Ohta, S., Kagawa, Y., Kondo, H., Kaneda, H., Yonekawa, H., Takai, D., and Miyabayashi, S.: "Nuclear but not mitochondrial genome involvement in human age-related mitochondrial dysfunction." J.Biol.Chem.269 (9). 6878-6883 (1994)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Hayashi, J-I., Ohta, S., Kagawa, Y., Takai, D., Miyabayashi, S., Tada, K., Nonaka, I.: "Functional and morphological abnormalities of mitochondria in human cells containing mitochondrial DNA with pathogenic point mutations in tRNA genes." J.Biol.Chem.269, (29). 19060-19066 (1994)
Description
「研究成果報告書概要(欧文)」より
