1997 Fiscal Year Final Research Report Summary
Analyzes of genes responsible for aging and the pathogenesis of diabetes by isolation of transgenic mice with pathogenic mtDNA mutation
| Project/Area Number |
07458226
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory animal science
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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 Associate Professor, 生物科学系, 助教授 (60142113)
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| Co-Investigator(Kenkyū-buntansha) |
YONEKAWA Hiromichi Department of Laboratory Animal Science, The Tokyo Metropolitan Institute of Med, 実験動物研究部門, 部長 (30142110)
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| Project Period (FY) |
1995 – 1997
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| Keywords | Mouse mtDNA / Mutation / Mitochondria knockout / Mitochondrial diseases / Diabetes mellitus / Aging |
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| Research Abstract |
We found that treatment with ditercalinium, an antitumor bis-intercalating agent, was extremely effective for completely excluding mtDNA in all the mouse cell lines we tested. The resulting mouse mtDNA-less (rho^0) cell lines were succesafully used for trapping mtDNA of living nerve cells into dividing cultured cells by fusion of the rho^0 cells with mouse brain synaptosomes, which represent synaptic endings isolated from nerve cells. The cybrid clones with neuronal mtDNA obtained all restored mitochondrial translation activity similarly irrespective of whether the mtDNA was derived from young or aged mice, suggesting that at least defects in mitochondrial genomes are not involved in the age-associated mitochondrial dysfunction observed in the brain of aged mice. Furthermore, we could trap a very small amount of a common 5823 bp-deletion mutant mtDNA (DELTAmtDNA^<5823>) that was detectable by PCR in the cybrid clones. As the amount of mutant mtDNA with large-scale deletions was expected to increase during prolonged cultivation of the cybrids, these cells should be available for establishment of mice containing the deletion mutant mtDNA.
Although we could not accomplish the main purpose of this project, our sucesss for isolation of rho^0 mouse cells would lead us to the isolation of mtDNA knockout mice.
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Research Products
(12 results)
