| Project/Area Number |
25460357
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TEZUKA Tohru 東京大学, 医科学研究所, 助教 (50312319)
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| Co-Investigator(Renkei-kenkyūsha) |
Yamanashi Yuji 東京大学, 医科学研究所, 教授 (40202387)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 神経科学 / 神経筋接合部 / シグナル伝達 / 神経筋疾患 / 神経筋シナプス / 筋無力症 |
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| Outline of Final Research Achievements |
The formation and maintenance of neuromuscular junctions (NMJs), a synapse essential for motoneural control of skeletal muscle contraction, is governed by the muscle-specific receptor-tyrosine kinase MuSK. Activation of MuSK involves Agrin, Lrp4, and Dok-7. Dok-7 is an essential muscle-intrinsic activator of MuSK. On the other hand, motor neuron-derived MuSK activator Agrin binds to MuSK’s co-receptor Lrp4 and indirectly activates MuSK. In the current study, by analysis of muscle-specific Dok-7 transgenic mice lacking Lrp4, we demonstrated that Lrp4 is required for efficient activation of MuSK by Dok-7 in vivo. In addition, using recombinant adeno-associated virus vectors carrying short hairpin RNAs targeting the mouse dok-7 gene, we showed that the correct, physiological level of dok-7 gene expression is critical for the postnatal maintenance of NMJs.
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