| Project/Area Number |
15390281
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | National Institute of Neuroscience, NCNP |
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Principal Investigator |
TAKEDA Shin'ichi National Institute of Neuroscience, NCNP, Department of Molecular Therapy, M.D., PHD., 遺伝子疾患治療研究部, 部長 (90171644)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Yuko National Institute of Neuroscience, NCNP, Department of Molecular Therapy, Section chief, 神経研究所・遺伝子疾患治療研究部, 室長 (00342931)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2005: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | α1-syntrophin / Dystrophin-Glycoprotein complex / tail suspention / knock out mice / nNOS / Muscle regeneration / muscle atrophy / satellite cells / ジストロフィン / mdx mice / DMD / オステオポンチン |
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| Research Abstract |
We previously identified abnormal muscle regeneration in α1-syntrophin knock-out mice (J.Cell Biol 158:1097-1107, 2002). These findings may represent abnormal muscle regeneration found in dystrophin-deficient Duchenne muscular dystrophy, since expression of α1-syntorophin, one of dystrophin-binding proteins, was also absent from the dystrophin-deficient sarcolemma. In this study, we further tried to elucidate molecular mechanism of muscle regeneration. We paticulaly paid attention on tail suspension model, where skeletal muscle was suffered from muscle atroply due to micro-gravity. Very interestingly those atrophied muscle revealed prompt recovery after re-loading on the ground. We intensively analyzed expression of constituents of dystrophin-glycoprotein complex (DGC) on the model. We found a decrease of expression of neuronal Nitric Oxide synthase (nNOS) from the sarcolemma during the tail suspension. nNOS is one of functional molecules, which is anchored to the sarcolemma through α1-syntrophin of DGC. Therefore, we examined process of tail suspension of both nNOS and α1-syntrophin knock out mice. Very interestingly, nNOS knock-out mice revealed resistency in muscle atrophy during tail suspension process, but α1-syntorophim knock-out mice did not. Moreover, nNOS knock-out mice showed difficulty in muscle regrowth in re-loading process. In muscle regrowth process, proliferation of satellite cells were most important, as found in muscle regeneration. We finally examined proliferation capacity of muscle satellite cells of nNOS knock out mice and revealed impaired proliferation capacity of these cells. Therefore, we concluded the expression of nNOS is very important both in muscle atrophy during tail suspension and in proliferation of satellite cells during muscle re-growth after reloading on the ground.
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