Clarification of new pathophysiological functions of CPI-17, an endogenous myosin phosphatase inhibitory protein.
| Project/Area Number |
25660224
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Veterinary medical science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HORI Masatoshi 東京大学, 農学生命科学研究科, 准教授 (70211547)
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| Co-Investigator(Renkei-kenkyūsha) |
KAKUTA Shigeru 東京大学, 大学院農学生命科学研究科, 准教授 (80345032)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 平滑筋 / ミオシン / リン酸化 / CPI-17 / 高血圧 / 収縮蛋白 / がん / ホスファターゼ / ゲノム編集 / 遺伝子改変マウス / 血管 / 消化管 / 気管 / フォスファターゼ |
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| Outline of Final Research Achievements |
Motility of smooth muscle cell is regulated by phosphorylation of myosin, which is modulated by myosin light chain kinase and myosin phosphatase. CPI-17 is an endogenous inhibitory protein of myosin phosphatase. Phosphorylated CPI-17 at Thr38 inhibits myosin phosphatase activity. The CPI-17 signaling is known to regulate pathophysiological functions such as hypertension, asthma and cancer in addition to regulate physiological functions such as blood pressure and intestinal motility and so on. However, production of mutant mice targeting CPI-17 were not succeeded in the world. In the present study, we approached to make mutant mice targeting CPI-17 by using CRISPR/Cas9 system. We succeeded to establish three mutant mice targeting CPI-17, CPI-17 knock-out, constitutive active CPI-17 (CA[T38E]CPI-17) knock-in and dominant negative CPI-17 (DN[T38A]CPI-17) knock-in mice. We started to clarify physiological and pathophysiological functions of CPI-17 by using these mutant mice.
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Report
(3 results)
Research Products
(7 results)
