2006 Fiscal Year Final Research Report Summary
Application of disease-model mice with mutant mtDNA for precise investigation of its pathogenesis
| Project/Area Number |
14GS0305
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| Research Category |
Grant-in-Aid for Creative Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Institution | University of Tsukuba |
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Principal Investigator |
HAYASHI Jun-Ichi University of Tsukuba, Graduate School of Life and Environmental Sciences, Professor (60142113)
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| Co-Investigator(Kenkyū-buntansha) |
YONEKAWA Hiromichi The Tokyo Metropolitan Institute of Medical Science, Department of Laboratory Animal Science, Vice President (30142110)
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| Project Period (FY) |
2002 – 2006
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| Keywords | mitochondrial diseases / mouse mtDNA mutation / disease model mice / gene therapy by nuclear transplantation / clone mice |
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| Research Abstract |
Purpose 1 : Precise investigation of pathogenesis.
Results : We provided first evidence that the mutated mtDNA is responsible for male infertility, which had been published in PNAS 103 : 15148-15153, 2006.
Purpose 2 : Transmission profiles of the mtDNA to following generations.
Results : It has been controversial of whether there is recombination in mammalian mtDNA. Our study provided convincing evidence that mouse mtDNA rarely recombine each other by creating mice carrying heteroplasmic mtDNAs, which had been published in PNAS 102 : 6057-6062, 2005. Moreover, we showed that the mitochondrial bottleneck is not generated due to a mtDNA copy number drastic decline in early oogenesis rather to a small effective number of segregation units for mtDNA in mouse germ cells, which had been published in Nature Genet. 39 : 386-390, 2007.
Purpose 3 : Development of gene therapy for mito-mice expressing respirtion defects.
Results : We can provide the first report of the success of gene therapy by application of nuclear transplantation technique to firtilized eggs of mito-mice, which had been published in PNAS 102 : 16765-16770, 2005.
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Research Products
(13 results)
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[Journal Article] Generation of trans-mitochondrial mice carrying homoplasmic mtDNAs with a missense mutation in a structural gene using ES cells2006
Author(s)
Kasahara A, Ishikawa K, Yamaoka M, Ito M, Watanabe N, Akimoto M, Sato A, Nakada K, Endo H, Suda Y, Aizawa S, Hayashi J.
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Journal Title
Hum Mol Genet 15(6)
Pages: 871-81
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Generation of trans-mitochondrial mice carrying homoplasmic mtDNAs with a missense mutation in a structural gene using ES cells.2006
Author(s)
Kasahara A, Ishikawa K, Yamaoka M, Ito M, Watanabe N, Akimoto M, Sato A, Nakada K Endo H, Suda Y, Aizawa S, Hayashi J.
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Journal Title
Mol Genet. 15(6)
Pages: 871-81
Description
「研究成果報告書概要(欧文)」より
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