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Analysis of the pathogenesis in hypertophic cardiomyopathy by using zebrafish models.

Research Project

Project/Area Number 25860589
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Cardiovascular medicine
Research InstitutionKanazawa University

Principal Investigator

Hodatsu Akihiko  金沢大学, 医学系, 協力研究員 (00623662)

Co-Investigator(Renkei-kenkyūsha) SEGUCHI OSAMU  国立循環器病研究センター, 病院, 医師 (60570869)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Keywords肥大型心筋症 / ゼブラフィッシュ / 遺伝子変異
Outline of Final Research Achievements

MYBPC3 antisense morpholino oligonucleotide (MO) and MYBPC3 mRNA were injected in one cell stage zebrafish embryos to assess the functional consequences of the MYBPC3 mutations found in human hypertrophic cardiomyopathy patients. Wild type MYBPC3 mRNA, wild type and A745D mutant mRNA, or double mutant mRNA (A745D and R815Q mutants) were co-injected. They corresponds wild type, single mutation (heterozygote) and compound heterozygote, respectively. Ventricular dimension
and heart rate were similar between the MYBPC3 MO group and the MYBPC3 MO with WT mRNA group or the MYBPC3 MO with Ala745Asp mRNA and WT mRNA group, whereas ventricular dimension and heart rate were significantly increased in the MYBPC3 MO with Ala745Asp mRNA and Arg815Gln mRNA group compared with the MYBPC3 MO group.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (11 results)

All 2016 2015 2014

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (5 results)

  • [Journal Article] Whole exome sequencing combined with integrated variant annotation prediction identifies a causative myosin essential light chain variant in hypertrophic cardiomyopathy.2016

    • Author(s)
      Nomura A, Tada H, Teramoto R, Konno T, Hodatsu A, Won HH, Kathiresan S, Ino H, Fujino N, Yamagishi M, Hayashi K.
    • Journal Title

      J Cardiol.

      Volume: 2 Issue: 2 Pages: 133-9

    • DOI

      10.1016/j.jjcc.2015.09.003

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Functional Characterization of Rare Variants Implicated in Susceptibility to Lone Atrial Fibrillation.2015

    • Author(s)
      Hayashi K, Konno T, Tada H, Tani S, Liu L, Fujino N, Nohara A, Hodatsu A, Tsuda T, Tanaka Y, Kawashiri MA, Ino H, Makita N, Yamagishi M.
    • Journal Title

      Circ Arrhythm Electrophysiol.

      Volume: 8 Issue: 5 Pages: 1095-1104

    • DOI

      10.1161/circep.114.002519

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Electrocardiographic QRS Fragmentation as a Marker for Myocardial Fibrosis in Hypertrophic Cardiomyopathy.2015

    • Author(s)
      Konno T, Hayashi K, Fujino N, Oka R, Nomura A, Nagata Y, Hodatsu A, Sakata K, Furusho H, Takamura M, Nakamura H, Kawashiri MA, Yamagishi M.
    • Journal Title

      J Cardiovasc Electrophysiol.

      Volume: 26 Issue: 10 Pages: 1081-1087

    • DOI

      10.1111/jce.12742

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Right ventricular hypertrophy is associated with cardiovascular events in hypertrophic cardiomyopathy: evidence from study with magnetic resonance imaging.2015

    • Author(s)
      Nagata Y, Konno T, Fujino N, Hodatsu A, Nomura A, Hayashi K, Nakamura H, Kawashiri MA, Yamagishi M.
    • Journal Title

      Can J Cardiol.

      Volume: 31 Issue: 6 Pages: 702-708

    • DOI

      10.1016/j.cjca.2014.12.036

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased extent of myocardial fibrosis in genotyped hypertrophic cardiomyopathy with ventricular tachyarrhythmias.2014

    • Author(s)
      Fujita T, Konno T, Yokawa J, Masuta E, Nagata Y, Fujino N, Funada A, Hodatsu A, Kawashiri MA, Yamagishi M, Hayashi K.
    • Journal Title

      J Cardiol.

      Volume: in press Issue: 1 Pages: 63-68

    • DOI

      10.1016/j.jjcc.2014.10.002

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Compound heterozygosity deteriorates phenotypes of hypertrophic cardiomyopathy with founder MYBPC3 mutation: evidence from patients and zebrafish models.2014

    • Author(s)
      Hodatsu A, Konno T, Hayashi K, Funada A, Fujita T, Nagata Y, Fujino N, Kawashiri MA, Yamagishi M.
    • Journal Title

      Am J Physiol Heart Circ Physiol.

      Volume: 307 Issue: 11 Pages: 1594-604

    • DOI

      10.1152/ajpheart.00637.2013

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Impact of Mutation Dosage on Phenotypes in Hypertrophic Cardiomyopathywith MYBPC3 Mutations; Evidence from Zebrafish Models.2015

    • Author(s)
      Akihiko Hodatsu, Tetsuo Konno, Kenshi Hayashi, Yoji Nagata, Ryota Teramoto, Noboru Fujino, Masa-aki Kawashiri, Masakazu Yamagishi
    • Organizer
      第79回日本循環器学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2015-04-24 – 2015-04-26
    • Related Report
      2014 Research-status Report
  • [Presentation] ミオシン結合タンパクC複合ヘテロ接合性変異によ る肥大型心筋症の重症表現型~臨床例・ゼブラフィッシュ を用いた検討~2015

    • Author(s)
      宝達 明彦, 田中 仁啓, 永田 庸二, 寺本 了太, 津田 豊暢, 今野 哲雄, 林 研至, 川尻 剛照, 藤野 陽, 山岸 正和
    • Organizer
      第112回日本内科学会講演会
    • Place of Presentation
      京都
    • Year and Date
      2015-04-10 – 2015-04-12
    • Related Report
      2014 Research-status Report
  • [Presentation] 第112回日本内科学会講演会2015

    • Author(s)
      宝達 明彦, 田中 仁啓, 永田 庸二, 寺本 了太, 津田 豊暢, 今野 哲雄, 林 研至, 川尻 剛照, 藤野 陽, 山岸 正和
    • Organizer
      ミオシン結合タンパクC複合ヘテロ接合性変異によ る肥大型心筋症の重症表現型~臨床例・ゼブラフィッシュ を用いた検討~
    • Place of Presentation
      京都
    • Year and Date
      2015-04-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] Impact of Compound Heterozygosity on Phenotypes of hypertrophic cardiomyopathy with MYBPC3 mutasions; Evidence from zebrafish models.2015

    • Author(s)
      Akihiko Hodatsu, Tetsuo Konno, Kenshi Hayashi, Ryota Teramoto, Yoji Nagata, Noboru Fujino, Masa-aki Kawashiri, Masakazu Yamagishi
    • Organizer
      American College of Cardiology 64th Annual Scientific Session
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2015-03-14 – 2015-03-16
    • Related Report
      2014 Research-status Report
  • [Presentation] A founder mutation of the myosin binding protein-C gene in hypertrophic cardiomyopathy and adverse outcomes with compound heterozygosity2014

    • Author(s)
      Akihiko Hodatsu, Tetsuo Konno, Kenshi Hayashi, Takashi Fujita, Yoji Nagata, Noboru Fujino, Masa-aki Kawashiri, Masakazu Yamagishi
    • Organizer
      European society of Cardiology Congress 2014
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2014-08-30 – 2014-09-03
    • Related Report
      2014 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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