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2000 Fiscal Year Final Research Report Summary

Generation and application of mtDNA knockout mice models of aging

Research Project

Project/Area Number 10832001
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 老化(加齢)
Research InstitutionUniversity of Tsukuba

Principal Investigator

HAYASHI Jun-ichi  University of Tsukuba, Institute of Biological Sciences Professor, 生物科学系, 教授 (60142113)

Project Period (FY) 1998 – 2000
KeywordsMouse mtDNA / mtDNA Mutation / Mitochondrial transfer / Aging model mice / mitochondrial tRNA
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.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Makiko Yamaoka: "Complete repopulation of mouse mtDNA-less cells with rat mtDNA restores mitochondrial translation but not mitochondrial respiratory function"Genetics. 155. 301-307 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masato Tawata: "A new mitochondrial DNA mutation at 14577 T/C is probably a major pathogenic mutation for maternally inherited type 2 diabetes"Diabetes. 49. 1269-1272 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiroshi Shitara: "Selective and continuous elimination of mitochondria microinjected into mouse eggs from spermatids, but not from liver cells, occurs throughout embryogenesis"Genetics. 156. 1277-1284 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimiko Inouc: "Generation of mice with mitochondrial dysfunction by introducing mouse mtDNA carrying a deletion into zygotes"Nature Genetics. 26. 176-181 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Eizo Ohkabo: "A patient with type 2 diabetes mellitus associated with mutations in sensing receptor gene and mitochondrial DNA"Biochem.Biophys.Res.Commun.. 278. 808-813 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yuko Aomi: "Cytoplasmic transfer of platelet mtDNA from eldery patient with Parkinson's disease to mtDNA-less Hela cells restores complete mitochondrial respiratory function"Biochem.Biophys.Res Commun.. 280. 265-273 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Makiko Yamaoka, Kotoyo Isoba, Hiroshi Shitara, Hiromichi Yonekawa, Shigeaki Miyabayashi, and Jun-Ichi Hayashi.: "Complete repopulation of mouse mitochondrial DNA-less cells with rat mitochondrial DNA restores mitochondrial translation but not mitochondrial respiratory function."Genetics. 155. 301-307 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masato Tawata, Jun-Ichi Hayashi, Kotoyo Isobe, Eizo Ohkubo, Masayuki Ohtaka, Jing Chen, Kaoru Aida, and Toshimasa Onaya.: "A new mitochondrial DNA mutation at 14577 T/C is probably a major pathogenic mutation of maternally inherited type 2 diabetes."Diabetes. 49. 1269-1272 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroshi Shitara, Hideki Kaneda, Akitsugu Sato, Kimiko Inoue, Atsuo Ogura, Hiromichi Yonekawa, and Jun-Ichi Hayashi.: "Selective and continuous elimination of mitochondria microinjected into mouse eggs from spermatids, but not from liver cells, occurs throughout embryogenesis."Genetics. 156. 1277-1284 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimiko Inoue, Kazuto Nakada, Atsuo Ogura, Kotoyo Isobe, Yu-ichi Goto, Ikuya Nonaka, and Jun-Ichi Hayashi.: "Generation of mice with mitochondrial dysfunction by introducing mouse mtDNA carrying a deletion into zygotes."Nature Genet. 26. 176-181 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Eizo Ohkubo, Kaoru Aida, Jing Chen, Jun-Ichi Hayashi, Kotoyo Isobe, Masato Tawata, Toshimasa Onaya.: "A patient with type 2 diabetes mellitus associated with mutations in calcium sensing receptor gene and mitochondrial DNA."Biochem. Biophys. Res. Commun.. 278. 808-813 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yuko Aomi, Chu-Shih Chen, Kazuto Nakada, Sayaka Ito, Kotoyo Isobe, Haruka Murakami, Shin-ya Kuno, Masato Tawata, Rumiko Matsuoka, Hidehiro Mizusawa, and Jun-Ichi Hayashi.: "Cytoplasmic transfer of platelet mtDNA from elderly patients with Parkinson's disease to mtDNA-less HeLa cells restores complete mitochondrial respiratory function."Biochem. Biophys. Res. Commun.. 280. 265-273 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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