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Studies on pathogeneses of mitochondrial DNA-based disorders

Research Project

Project/Area Number 23240058
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionUniversity of Tsukuba

Principal Investigator

NAKADA Kazuto  筑波大学, 生命環境系, 教授 (80323244)

Project Period (FY) 2011-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥45,890,000 (Direct Cost: ¥35,300,000、Indirect Cost: ¥10,590,000)
Fiscal Year 2015: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2014: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Fiscal Year 2013: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Fiscal Year 2012: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Fiscal Year 2011: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Keywordsミトコンドリア / ミトコンドリアDNA / 突然変異 / ミトコンドリア呼吸機能異常 / ミトコンドリア病 / モデルマウス / ミトコンドリアゲノム / エネルギー代謝 / ミトコンドリアゲノム変異 / エネルギー欠損 / 病態モデルマウス / エネルギー代謝不全 / 病態発症機構
Outline of Final Research Achievements

The aim of this study was to clear multiple pathogeneses of mitochondrial DNA (mtDNA)-related disorders by using model mice carrying mutant mtDNAs. As results, 1) we succeeded in generating novel model mice carrying mtDNA with a point mutation in tRNA-Lys gene, and the mice expressed myopathy due to the accumulation of mtDNA with a point mutation in tRNA-Lys gene; 2) we showed that mtDNA with a point mutation in ND6 gene was responsible for age-related lymphoma in mice; 3) the diabetic condition was a possible modifier to enhance the pathogenicity of mutant mtDNAs.

Report

(6 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (33 results)

All 2015 2014 2013 2012 2011 Other

All Journal Article (18 results) (of which Peer Reviewed: 18 results,  Open Access: 7 results,  Acknowledgement Compliant: 5 results) Presentation (11 results) (of which Invited: 8 results) Remarks (4 results)

  • [Journal Article] Mouse somatic mutation orthologous to MELAS A3302G mutation in the mitochondrial tRNA(Leu(UUR)) gene confers respiration defects.2015

    • Author(s)
      Shimizu A, Enoki S, Ishikawa K, Mito T, Obata K, Nagashima R, Yonekawa H, Nakada K, Hayashi J.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 467 Issue: 4 Pages: 1097-102

    • DOI

      10.1016/j.bbrc.2015.09.072

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defects2015

    • Author(s)
      Hashizume O, Ohnishi S, Mito T, Shimizu A, Ishikawa K, Nakada K, Soda M, Mano H, Togayachi S, Miyoshi H, Okita K, Hayashi J
    • Journal Title

      Sci Rep

      Volume: 5 Issue: 1 Pages: 10434-10434

    • DOI

      10.1038/srep10434

    • NAID

      120005819481

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A somatic T15091C mutation in the Cytb gene of mouse mitochondrial DNA dominantly induces respiration defects.2015

    • Author(s)
      Hayashi C, Takibuchi G, Shimizu A, Mito T, Ishikawa K, Nakada K, Hayashi JI
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 463 Issue: 4 Pages: 1021-1027

    • DOI

      10.1016/j.bbrc.2015.06.052

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Novel MitoNEET Ligand, TT01001, Improves Diabetes and Ameliorates Mitochondrial Function in db/db Mice2015

    • Author(s)
      Takehiro Takahashi, Masashi Yamamoto, Kazutoshi Amikura, Kozue Kato, Takashi Serizawa,Kanako Serizawa, Daisuke Akazawa, Takumi Aoki, Koji Kawai, Emi Ogasawara, Jun-Ichi Hayashi, Kazuto Nakada, and Mie Kainoh
    • Journal Title

      J. Pharmacol. Exp. Ther.

      Volume: 352 Issue: 2 Pages: 338-345

    • DOI

      10.1124/jpet.114.220673

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Transmitochondrial mito-miceΔ and mtDNA mutator mice, but not aged mice, share the same spectrum of musculoskeletal disorders.2015

    • Author(s)
      Mito T, Ishizaki H, Suzuki M, Morishima H, Ota A, Ishikawa K, Nakada K, Maeno A, Shiroishi T, Hayashi J-I
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 456 Issue: 4 Pages: 933-937

    • DOI

      10.1016/j.bbrc.2014.12.009

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] G7731A mutation in mouse mitochondrial tRNALys regulates late-onset disorders in transmitochondrial mice.2015

    • Author(s)
      Shimizu A, Mito T, Hashizume O, Yonekawa H, Ishikawa K, Nakada K, Hayashi J-I
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 459 Issue: 1 Pages: 66-70

    • DOI

      10.1016/j.bbrc.2015.02.070

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Specific Nuclear DNA Background Is Required for High Frequency Lymphoma Development in Transmitochondrial Mice with G13997A mtDNA2015

    • Author(s)
      Osamu Hashizume, Haruka Yamanashi, Makoto M. Taketo, Kazuto Nakada, and Jun-Ichi Hayashi
    • Journal Title

      PLoS ONE

      Volume: 10 Issue: 3 Pages: e0118561-e0118561

    • DOI

      10.1371/journal.pone.0118561

    • NAID

      120007130305

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Administration of an Antioxidant Prevents Lymphoma Development in Transmitochondrial Mice Overproducing Reactive Oxygen Species2014

    • Author(s)
      Haruka Yamanashi, Osamu Hashizume, Hiromichi Yonekawa, Kazuto Nakada, and Jun-Ichi Hayashi
    • Journal Title

      Exp. Anim.

      Volume: 63 Pages: 459-466

    • NAID

      130004701643

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Selection of rodent species appropriate for mtDNA transfer to generate transmitochondrial mito-mice expressing mitochondrial respiration defects.2014

    • Author(s)
      Enoki S, Shimizu A, Hayashi C, Imanishi H, Hashizume O, Mekada K, Suzuki H, Hashimoto T, Nakada K, Hayashi J
    • Journal Title

      Exp Anim

      Volume: 63 Pages: 21-30

    • NAID

      130003391604

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transmitochondrial mice as models for primary prevention of diseases caused by mutation in the tRNA(Lys) gene.2014

    • Author(s)
      Shimizu A, Mito T, Hayashi C, Ogasawara E, Koba R, Negishi I, Takenaga K, Nakada K, Hayashi J
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 111 Issue: 8 Pages: 3104-3109

    • DOI

      10.1073/pnas.1318109111

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Specific mtDNA mutations in mouse carcinoma cells suppress their tumor formation via activation of the host innate immune system.2013

    • Author(s)
      Imanishi H, Takibuchi G, Kobayashi T, Ishikawa K, Nakada K, Mori M, Kikkawa Y, Takenaga K, Toyama-Sorimachi N, Hayashi J
    • Journal Title

      PLoS One

      Volume: 8 Issue: 9 Pages: e75981-e75981

    • DOI

      10.1371/journal.pone.0075981

    • NAID

      120007136806

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Polymorphic mutations in mouse mitochondrial DNA regulate a tumor phenotype.2013

    • Author(s)
      Takibuchi G, Imanishi H, Morimoto M, Ishikawa K, Nakada K, Toyama-Sorimachi N, Kikkawa Y, Takenaga K, Hayashi J
    • Journal Title

      Mitochondrion

      Volume: 13 Issue: 6 Pages: 881-887

    • DOI

      10.1016/j.mito.2013.07.117

    • NAID

      120007130592

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mitochondrial DNA with a large-scale deletion causes two distinct mitochondrial disease phenotypes in mice.2013

    • Author(s)
      Katada S, Mito T, Ogasawara E, Hayashi J, Nakada K
    • Journal Title

      G3 (Bethesda)

      Volume: 3 Issue: 9 Pages: 1545-1552

    • DOI

      10.1534/g3.113.007245

    • NAID

      120007136822

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mitochondrial DNA mutations in mutator mice confer respiration defects and B-cell lymphoma development.2013

    • Author(s)
      Takayuki Mito, Yoshiaki Kikkawa, Akinori Shimizu, Osamu Hashizume, Shun Katada, Hirotake Tmaniahi Azusa Ota, Yukina Kato, Kazuto Nakada, Jun-Ichi Hayashi.
    • Journal Title

      PLoS One

      Volume: 8(2) Issue: 2 Pages: e55789-e55789

    • DOI

      10.1371/journal.pone.0055789

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Specific mitochondrial DNA mutation in mice regulates diabetes and lymphoma development2012

    • Author(s)
      Hashizume O, Shimizu A, Yokota M, Sugiyama A, Nakada K, Miyoshi H, Itami M, Ohira M, Nagase H, Takenaga K, Hayashi J.
    • Journal Title

      Proc Natl Acad Sci USA.

      Volume: 109(26) Issue: 26 Pages: 10528-33

    • DOI

      10.1073/pnas.1202367109

    • NAID

      120007137266

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transmitochondrial mice as models for mitochondrial DNA-based diseases2011

    • Author(s)
      Nakada, K.
    • Journal Title

      Experimental Animals

      Volume: 60 Pages: 421-431

    • NAID

      10029835173

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nuclear but Not Mitochondrial DNA Involvement in Respiratory Complex I Defects Found in Senescence-Accelerated Mouse Strain, SAMP82011

    • Author(s)
      Imanishi, H.
    • Journal Title

      Experimental Animals

      Volume: 60 Pages: 397-404

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mitochondrial DNA mutations regulate metastasis of human breast cancer cells2011

    • Author(s)
      Imanishi, H.
    • Journal Title

      PLoS One

      Volume: 6

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] ミトコンドリアゲノム変異のマウス逆遺伝学~ミトコンドリアダイナミクスと病態発症調節~2015

    • Author(s)
      中田和人
    • Organizer
      第15回日本ミトコンドリア学会年会
    • Place of Presentation
      福井県福井市
    • Year and Date
      2015-11-20
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 突然変異型ミトコンドリアゲノムのマウス逆遺伝学2015

    • Author(s)
      中田和人
    • Organizer
      日本遺伝学会第87回大会
    • Place of Presentation
      宮城県仙台市
    • Year and Date
      2015-09-24
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] ミトコンドリアセントラルドグマの破綻病理~多様な病型形成機構の理解に向けて~2015

    • Author(s)
      中田和人
    • Organizer
      第119回日本眼科学会総会
    • Place of Presentation
      北海道札幌市
    • Year and Date
      2015-04-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] ミトコンドリアセントラルドグマの破綻病理に関する基礎研究2014

    • Author(s)
      中田和人
    • Organizer
      国立遺伝学研究所研究集会~オルガネラゲノムに支配される生命現象~
    • Place of Presentation
      国立遺伝学研究所(静岡県三島市)
    • Year and Date
      2014-11-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 突然変異型ミトコンドリアゲノムの病原性制御~ミトコンドリア・ダイナミクスの関与~2014

    • Author(s)
      中田和人、石原直忠、林純一
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2014-10-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] ミトコンドリア遺伝子疾患の病態発現機構2014

    • Author(s)
      中田和人
    • Organizer
      アディポ・サイエンスシンポジウム
    • Place of Presentation
      千里ライフサイエンスセンター(大阪府豊中市)
    • Year and Date
      2014-08-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Model mouse studies: Regulation of threshold effects on pathogenesis of mitochondrial DNA-based disease2014

    • Author(s)
      Kazuto Nakada
    • Organizer
      Euromit 2014
    • Place of Presentation
      Tampere, Finland
    • Year and Date
      2014-06-15
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Reverse genetic studies on mutant mitochondrial genomes in mice2013

    • Author(s)
      Kazuto Nakada and Jun-Ichi Hayashi
    • Organizer
      The 4th International Symposium on Dynamics of Mitochondria (DynaMito2013)
    • Place of Presentation
      Okinawa Zanpamisaki Royal Hotel, Okinawa, Japan
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Reverse genetic studies on mammalian mtDNA mutations2011

    • Author(s)
      Nakada, K.
    • Organizer
      The Eighth European Meeting on Mitochondrial Pathology
    • Place of Presentation
      ザラゴザ、スペイン(招待講演)
    • Year and Date
      2011-06-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] ミトコンドリア糖尿病のマウス逆遺伝学

    • Author(s)
      中田和人
    • Organizer
      第85回日本生化学会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] 病原性ミトコンドリアゲノム変異のマウス逆遺伝学

    • Author(s)
      中田和人
    • Organizer
      第55回日本腎臓学会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2012 Annual Research Report
  • [Remarks] 筑波大学生命環境系 中田ー石川研究室

    • URL

      http://www.biol.tsukuba.ac.jp/~jih-kzt/

    • Related Report
      2015 Annual Research Report
  • [Remarks]

    • URL

      http://www.biol.tsukuba.ac.jp/~jih-kzt/

    • Related Report
      2014 Annual Research Report
  • [Remarks] Jun-Ichi Hayashi + Kazuto Nakada's Lab

    • URL

      http://www.biol.tsukuba.ac.jp/~jih-kzt/

    • Related Report
      2013 Annual Research Report
  • [Remarks] Jun-Ichi Hayashi + Kazuto Nakada's Lab

    • URL

      http://www.biol.tsukuba.ac.jp/~jih-kzt/

    • Related Report
      2012 Annual Research Report

URL: 

Published: 2011-04-06   Modified: 2019-07-29  

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