| Project/Area Number |
07557012
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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 |
General pharmacology
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| Research Institution | The University of Tokyo (1996-1997)
Kyushu University (1995) |
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Principal Investigator |
MOTOYA Katsuki The Institute of Medical Science The University of Tokyo, Professor, 医科学研究所, 教授 (20051732)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Minesuke Mitsubishi Kasei Institute of Life Sciences, Chief, 生殖研究室, 室長
NAKAO Kazuki The Institute of Medical Science The University of Tokyo, Research Associate, 医科学研究所, 寄付研究部員教員 (20217657)
NAKAMURA Kenji The Institute of Medical Science The University of Tokyo, Research Associate, 医科学研究所, 助手 (90253533)
AIBA Atsu The Institute of Medical Science The University of Tokyo, Associate Professor, 医科学研究所, 助教授 (20271116)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥15,200,000 (Direct Cost: ¥15,200,000)
Fiscal Year 1997: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1996: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1995: ¥8,200,000 (Direct Cost: ¥8,200,000)
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| Keywords | animal models / pharmacology / serotonin receptor / serotonin / gene targeting / gene replacement / ES cell / humanized mouse / ジーンターゲッテイング |
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| Research Abstract |
An experiment using animal models is one of the most important projects for pharmacological studies. The development of novel drugs, in which the action should first be proved theoretically, may be possible by performing experiments using animal models. However, there are almost always. some differences between humans and animals Although serotonin acts through serotonin receptors, the mouse serotonin receptor 1B does not respond to either the agonists or antagonists developed for human serotonin receptor 1B.This difference was overcome by changing the 355th amino acid residue, threonin, of the human protein to aspargine, which is the equivalent residue of the mouse protein This means that even the single amino acid difference between humans and animals thus made it impossible to extrapolate the results from animal experiments to human beings.
We developed novel methods to replace the target gene with the desired sequences, such as a point mutation, small deletion, or human homologue, without any marker genes. In this study, we applied this method to the serotonin receptor 1B gene. We thereby succeeded in making the ES cell lines which carry the humanized serotonin 1B gene in place of the mouse gene .Chimera mice were also produced and we are now looking forward to obtaining the offspring of this germ line transmission.
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