| Project/Area Number |
08557047
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | University of Tokyo |
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Principal Investigator |
ISHIKAWA Takashi (1998) University of Tokyo, Third Department of Internal Medicine, Research Associate, 医学部・附属病院, 助手 (50202958)
山沖 和秀 (1997) 東京大学, 医学部・附属病院, 講師 (70182409)
矢崎 義雄 (1996) 東京大学, 医学部・附属病院, 教授 (20101090)
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| Co-Investigator(Kenkyū-buntansha) |
KATOH Hirohisa Yamasa Company, Second Laboratory, Research Associate, 研究開発部・生物研究室, 研究員
SUZUKI Toru University of Tokyo, Third Department of Internal Medicine, Research Associate, 医学部, 医員
SHIOJIMA Ichiro University of Tokyo, Third Department of Internal Medicine, Research Associate, 医学部, 助手
小室 一成 東京大学, 医学部・附属病院, 助手 (30260483)
山沖 和秀 東京大学, 医学部・附属病院, 講師 (70182409)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥17,000,000 (Direct Cost: ¥17,000,000)
Fiscal Year 1998: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1997: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1996: ¥10,600,000 (Direct Cost: ¥10,600,000)
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| Keywords | Csx / GATA-4 / ANP / transgenic mouse / Zf11 / ホメオボックス / マウス / 心臓 / two-hybrid system / CSX / 心筋 / 発生 / COS-7細胞 / 転写 |
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| Research Abstract |
A murine cardiac homeodomain gene Csx/Nkx-2.5 plays an essential role in the heart development. To examine the function of CSX in in viva context, we generated transgenic mice overexpressing CSX, a human homolog of Csx under the control of CMV enhancer/chicken beta-actin promoter. The transgene was expressed abundantly in the heart and moderately in the skeletal muscle. The transgenic mice overexpressing CSX were viable and fertile without growth retardation nor signs of heart failure. There was no significant difference in left ventricular weight to body weight ratio or systolic arterial blood pressure between the transgenic mice and the wild type litter mates. Ultrasonic echocardiography showed no significant difference in cardiac function and wall thickness. Northern blot analysis revealed that mRNA levels of ANP, BNP and CARP genes were more abundant in the ventricle of transgenic mice than that of wild type mice. Endogenous murine Csx mRNA levels were also up-regulated in the heart of transgenic mice, suggesting the existence of positive auto-regulatory loop in transcription of Csx gene. Electromicroscopic analysis showed that there are many secretory granules in the left ventricular myocardium of the transgenic mice, but not of wild type mice. It has been reported that ANP is secreted constitutively in the ventricle, while in the atrium, regulated secretion is operated. Therefore, it is noteworthy that regulated secretion mechanism may be induced in the ventricle of the CSX transgenic mice. There are two possibilities in the formation of secretory granules. First, CSX induces abundant expression of ANP, resulting in induction of granule-forming proteins. Second possibility is that CSX directly induces expression of granule-forming proteins. Further investigation is necessary to elucidate these possibilities.
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