2000 Fiscal Year Final Research Report Summary
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
| Project/Area Number |
11470005
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General anatomy (including Histology/Embryology)
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
SHIBATA Yosaburo Faculty of Medical Sciences KYUSHU UNIVERSITY, Professor, 大学院・医学研究院, 教授 (90037482)
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| 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)
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| Project Period (FY) |
1999 – 2000
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| Keywords | connexin / gap junction / gene targeting / lacZ / NFATC1 / endocardial cushion / heart / A-V block |
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| 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.
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Research Products
(12 results)
