| Project/Area Number |
10832001
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
老化(加齢)
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| Research Institution | University of Tsukuba |
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Principal Investigator |
HAYASHI Jun-ichi University of Tsukuba, Institute of Biological Sciences Professor, 生物科学系, 教授 (60142113)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Mouse mtDNA / mtDNA Mutation / Mitochondrial transfer / Aging model mice / mitochondrial tRNA / マウス / 老化 / ミトコンドリアDNA / 突然変異 / 遺伝子導入 / 病態モデルマウス / 呼吸欠損 / 神経変性疾患 / 核移植 / ミトコンドリアノックアウト / ミトコンドリア間相互作用 |
|---|
| Research Abstract |
Mice possessing pathogenic mutant mitochondrial DNA (mtDNA) would provide ideal systems for studying exactly how mutant mtDNAs are transmitted and distributed in tissues resulting in expression of mitochondrial diseases, but no effective procedures are available for their generation. Isolation of mtDNA-less (ρ^0) mouse cells enabled us to trap mouse mutant mtDNAs that had accumulated in somatic tissues into mtDNA repopulated ρ^0 cells (cybrids). We could isolate respiration-deficient cybrids with a deletion mutant mtDNA and introduce it into fertilized eggs. The mutant mtDNA was transmitted maternally, and its accumulation induced mitochondrial dysfunction in various tissues. Moreover, most of these mice unexpectedly died as a consequence of renal failure, suggesting the involvement of mtDNA mutations in the pathogeneses of new diseases.
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