Analysis of cave-in-3/nNOS w-null mice
| Project/Area Number |
24591281
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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 |
Neurology
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Tatsufumi 川崎医科大学, 医学部, 准教授 (30330591)
OHSAWA Yutaka 川崎医科大学, 医学部, 講師 (80246531)
大澤 裕 川崎医科大学, 医学部, 講師 (80246511)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 筋ジストロフィー / 再生医療 / シグナル伝達 / 国際情報交換 / カベオリン-3 / 神経型NO合成酵素（nNOS) / 筋萎縮 |
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| Outline of Final Research Achievements |
Caveolin, an intergal membrane protein of the plasma membrane caveolae, binds to and regulates nitric oxide synthases (NOS) in several cells and tissues. However, interaction of caveolin-3 and neuronal NOS (nNOS) in myofiber has remained unknown. We previously generated a model of limb-girdle muscular dystrophy by overexpressing the disease-causing mutant caveolin-3 (CAV-3P104L) in skeletal muscle. Loss of caveolin-3 resulted in atrophic myopathy with increased sarcolemmal nNOS activity, indicating caveolin-3 binding and suppression on nNOS in myofiber. Here, we generated and characterized the double mutant mice showing both deficiency of nNOS and loss of caveolin-3 (CAV-3P104L+/+, nNOS-/-). The double-mutant mice exhibited a reduction in the muscle mass and strength in comparison with the mutant caveolin-3 mice. Thus, increased sarcolemmal nNOS activity by the loss of caveolin-3 could prevent muscle atrophy in the pathogenesis leading to LGMD1C.
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Identification of the minimum peptide from mouse myostatin prodomain for human myostatin inhibition.2015
Author(s)
Takayama K, Noguchi Y, Aoki S, Takayama S, Yoshida M, Asari T, Yakushiji F, Nishimatsu S, Ohsawa Y, Itoh F, Negishi Y, Sunada Y, Hayashi Y
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Journal Title
J Med Chem
Volume: 58
Issue: 3
Pages: 1544-1549
DOI
Related Report
Peer Reviewed
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[Journal Article] An inhibitor of transforming growth factor beta type I receptor ameliorates muscle atrophy in a mouse model of caveolin 3-deficient muscular dystrophy2012
Author(s)
Ohsawa Y, Okada T, Nishimatsu SI, Ishizaki M, Suga T, Fujino M, Murakami T, Uchino M, Tsuchida K, Noji S, Hinohara A, Shimizu T, Shimizu K, Sunada Y
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Journal Title
Lab Invest
Volume: 78
Issue: 8
Pages: 1100-1114
DOI
Related Report
Peer Reviewed
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