| Project/Area Number |
12671099
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Gunma University |
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Principal Investigator |
TOMURA Hideaki Gunma University, Institute for Molecular and Cellular Regulation, Research Associate, 生体調節研究所, 助手 (70217553)
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| Co-Investigator(Kenkyū-buntansha) |
SHO Kimie Gunma University, Institute for Molecular and Cellular Regulation, Research Assistant, 生体調節研究所, 教務員 (40201561)
TAKEDA Jun Gunma University, Institute for Molecular and Cellular Regulation, Professor, 生体調節研究所, 教授 (40270855)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | MODY / HNF-1β / Transgenic mouse |
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| Research Abstract |
Hepatocyte nuclear factor-1α (HNF-1α) and HNF-1β are transcriptional activator proteins and belong to the same homeoprotein family. The mutations of these genes are responsible for maturity onset diabetes of the young 3 (MODY3) and MODY5, respectively. HNF-1α and HNF-1β can form homo- or hetro-dimer and bind to the same target DNA sequences in vitro. On the other hand, a decrease of HNF-1α expression in mouse caused glucose intolerance but a decrease of HNF-1β expression in mouse did not. So, we hypothesize that the dominant negative effect of HNF-1β but not HNF-1α mutation is crucial for development of MODY. In this study, we aim to make a transgenic mouse that over-expresses a dominant-negative HNF-1β mutant protein and try to elucidate the mechanism for the develomnent of MODY5. In the term of this project, we made some vectors by which the dominant-negative HNF-1β mutant protein could be expressed and injected these vectors to some fertilized mouse eggs. Unfortunately, however, we can not get any positive transgenic mouse until now. The reason is that the vectors would not be suitable for the expression in mouse, or that the expression of the mutant protein would have some toxic effects on the development of mouse embryo. Now we are checking about these possibilities. In relation to the vector, we recently succeed to make a transgenic mouse that over-expresses a kind of amino acid transporter in β cell specifically. So we plan to change the mutant HNF-1β cDNA to this vector which we used for the injection to express the amino acid transporter.
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