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ギャップ結合蛋白遺伝子変異マウスの分子解剖学的研究

Research Project

Project/Area Number 11470005
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field General anatomy (including Histology/Embryology)
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

SHIBATA Yosaburo  Faculty of Medical Sciences KYUSHU UNIVERSITY, Professor, 大学院・医学研究院, 教授 (90037482)

Co-Investigator(Kenkyū-buntansha) NISHII Kiyomasa  Faculty of Medical Sciences KYUSHU UNIVERSITY, Reserch Associate, 大学院・医学研究院, 助手 (20264020)
INAI Tetsuichiro  Faculty of Medical Sciences KYUSHU UNIVERSITY, Lecturer, 大学院・医学研究院, 講師 (00264044)
NAKAMURA Keiichiro  Faculty of Medical Sciences KYUSHU UNIVERSITY, Associate Prof., 大学院・医学研究院, 助教授 (20172398)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 2000: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥10,700,000 (Direct Cost: ¥10,700,000)
Keywordsconnexin / gap junction / gene targeting / lacZ / NFATC1 / endocardial cushion / heart / A-V block / Cre-loxP system / NF-ATcl
Research Abstract

We created mice harboring an nls-lacZ gene in place of connexin45, which encodes the only known gap junction protein in the primitive heart before embryonic dey 9, using the cre-loxPsystem. Heterologous recombinant mice revealed Lac Z signals in the nucleus in various tissues : some nuclei in the brain, retina, intestinal and vascular smooth muscles, endothelial cells of blood vessels and endocardium, and impulse conducting fibers of the heart. Connexin45-deficient mice died of heart failure at around embryonic day 10. They initiated heart contractions, but conduction block appeared ithin 24 hours after the first contractions. Their cardiac walls displayed an endocardial cushion defect, while the cardiac jelly was present. These abnormalities were caused by impairment of the epithelial-mesenchymal transformation of the cardiac endothelium. Activation of the endothelium depended on the presence of the connexin45 gap junctions since signaling through Ca^<2+>/calcineurin and NF-ATcl (originally named NF-ATc)was disrupted in the mutant hearts. These results indicate a requirement for gap junction intercellular channels during early cardiogenesis and hence implicate connexin in congenital heart diseases. This finding may be the first report to present the direct molecular mechanism of cell to cell communication through gap junction in the tissue development.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] K.Nakamura et al.: "Connexin43 exprssion in network-forming cells at the submuscosal-muscular border of guinea pig and dog colon."Cells tissues Organs (Acta Anat)). 165. 16-21 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Toma et al.: "Three-dimensional structures of c-kit-positive cellular networks in the guinea pig small intestine and colon."Cell Tissue Res. 295. 425-436 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Nakamura et al.: "Distoribution of gap junction protein connexin37 in smooth muscle cells of the rat trachea and pulmonary artery."Arch.histol.Cytol.. 62・1. 27-37 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Inai et al.: "Claudin-1 contributes to the epithelial barrier function in MDCK cells."Eur.J.Cell Biol.. 78. 849-855 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Nishii et al.: "Abnormalities of developmental cell death in Dad1-deficient mice."Genes to Cells. 4. 243-252 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Kumai et al.: "Loss of connexin45 causes a cushion defect in early cardiogenesis."Development. 127. 3501-3512 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Nakamura, Y.Shibata: "Connexin43 expression in network-forming cells at the submuscosal-muscular border of guinea pig and dog colon."Cells tissues Organs (Acta Anat). 165. 16-21 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Toma, K.Nakamura, A.Kuraoka, M.Tanaka, M.Kawabuchi: "Three-dimensional structures of c-kit-positive cellular networks in the guinea pig small intestine and colon."Cell Tissue Res. 295. 425-436 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Nakamura, T.Inai, K.Nakamura, Y.Shibata: "Distoribution of gap junction protein connexin37 in smooth muscle cells of the rat trachea and pulmonary artery."Arch Histor Cytol. 62 (1). 27-37 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Inai, J.Kobayashi, Y.Shibata: "Claudin-1 contributes to the epithelial barrier function in MDCK cells"Eur J Cell Biol. (78). 849-855 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Nishii, Tsuzuki.T, M.Kumai, N.Takeda, H.Koga, S.Aizawa, T.Nishimoto, Y.Shibata.: "Abnormalities of developmental cell death in Dad1-deficient mice"Genes Cells. 4. 243-252 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Kumai, K.Nishii, K.Nakamura, N.Takeda, M.Suzuki, Y.Shibata.: "Loss of connexin45 causes a cushion defect in early cardiogenesis."Development. 127. 3501-3512 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Kumai et al.: "Loss of connexin45 causes a cushion defect in early cardiogenesis."Development. 127. 3501-3512 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K. Nakamura et al.: "Connexin43 expression in network-forming cells at the submuscular-mucular border of the guinea pig and dog colon."Cells Tissues Organs. 165. 16-21 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K. Nakamura et al.: "Dostribution of gap junction protein Connexin 37 in smooth muscle cells of the rat trachea and pulmonary artery."Arch.Histol.Cytol.. 62. 27-37 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T. Inai et al.: "Claudin-1 contributes to the epithelial barrier function in MDCK cells."Eur.J.Cell Biol.. 78. 849-855 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K. Nakamura et al.: "Abnormalities of developmental cell death in Dad1-deficient mice."Genes Cells. 4・4. 243-252 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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