• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

1998 Fiscal Year Final Research Report Summary

Molecular mechanism of HCM caused by mutation in the cardiac TnT gene.

Research Project

Project/Area Number 09670771
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKURUME UNIVERSITY

Principal Investigator

NAKATA Masashi  Kurume University, School of Medicine, Assistant Professor, 医学部, 講師 (70180304)

Co-Investigator(Kenkyū-buntansha) NAKAURA Hiroyuki  Kurume University, School of Medicine, Instructor, 医学部, 助手 (50279171)
IWAMI Gensho  Kurume University, School of Medicine, Assistant Professor, 医学部, 講師 (90203405)
NISHI Hirofumi  Kurume University, School of Medicine, Assistant Professor, 医学部, 講師 (60189248)
Project Period (FY) 1997 – 1998
KeywordsHypertrophic cardiomyopathy / Troponin T / Skinned fiber / Splice-donor site mutation / Calcium sensitivity
Research Abstract

A splice donor site mutation in intron 15 of the cardiac troponin T (TnT) gene has been shown to cause familial hypertrophic cardiomyopathy (HCM) and the translation of the aberrant mRNAs resulting from this mutation is expected to produce two truncated mutant molecules lacking carboxyl terminus to different extent. In this study, wild-type and two truncated human cardiac TnTs were expressed in E.coli and directly exchanged into rabbit permeabilized cardiac muscle fibers to determinine the functional consequence of this HCM-causing mutation. The skinned fibers exchanged with short truncated TnT generated a slightly lower Ca^<2+>-activated maximum force compared to the fibers exchanged with wild-type TnT, which is qualitatively consistent with the finding on a transfected quail skeletal myotube expressing this mutant TnT.On the other hand, long truncated TnT had no effect on the maximum force-generating capacity. Both these two truncated human cardiac TnTs conferred a lower cooperativity and high Ca^<2+> sensitivity on the Ca^<2+> activation of skkined cardiac muscle than wild-type TnT.The results provide evidence that an increased Ca^<2+> sensitivity and decreased cooperativity in the activation of cardiac myofilament may be involved in the pathogenesis of HCM caused by this splice donor site mutation in the cardiac TnT gene.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] 中田 真詩: "心筋炎の疫学、予後、自然歴" Heart View. 6. 86-92 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中田 真詩: "肥大型心筋症研究の最近のあゆみ" 臨床成人病. 28. 559-565 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中田 真詩: "高血圧性心臓病" 臨床と研究. 75. 2369-2373 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishi H: "Expression of proto-oncogene and gene mutation of sarcomeric protein in patients with hypertrophic cardiomyopathy" Circulation Research. 83. 594-601 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 西 宏文: "HCMの異常肥大のメカニズム" Heart View. 4. 467-470 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中田 真詩: "心筋トロポニンT遺伝子異常肥大型心筋症の発症機序に関する生理学的検討" 日本循環器学会誌. 62. 264- (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中田 真詩: "KEY WORD 1999-2000 高血圧" 先端医学社, 280 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Nakata: "Epidemiology, Prognosis and Natural history of Myocarditis (in japanese)" Heart View. No6. 86-92 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Nakata: "Review in reseach of hypertrophic Cardiomyopathy (in japanese)" Rinsyo seijinnbyo. No28. 559-565 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Nakata: "Hypertensive heart disease (in japanese)" Clinical and Reseach. No75. 2369-2373 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Nishi: "Expression of proto-oncogene and gene mutation of sarcomeric protein in patients with HCM" Circ.Res.83. 594-601 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Nakata: "Physiological mechanism in expression of cardiac troponin T HCM (in japanese)" Jpn.Cic.J. 62. 264 (1998)

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

URL: 

Published: 1999-12-08  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi