| Project/Area Number |
25860306
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Experimental pathology
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| Research Institution | National Center of Neurology and Psychiatry |
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Principal Investigator |
TANIHATA Jun 独立行政法人国立精神・神経医療研究センター, 神経研究所 遺伝子疾患治療研究部, 流動研究員 (00508426)
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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 |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 筋ジストロフィー / 筋小胞体 / SERCA / ｎＮＯＳ / カルシウム動態 / 細胞内カルシウム動態 / 短縮型ジストロフィン / nNOS / 細胞内カルシウム濃度 / リアノジン受容体 |
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| Outline of Final Research Achievements |
Duchenne muscular dystrophy (DMD) is caused by lack of dystrophin. Exon skipping is a promising treatment for DMD and “exon 45-55 skipping” strategy is though to be one of the goals of this therapy, partly because Becker muscular dystrophy patients with exon 45-55 in-frame deletion show very mild skeletal muscle symptoms. However the function of exon 45-55 deleted dystrophin is not well investigated. We generated Tg/mdx mice and extensively analyzed their phenotypes. The improvement of muscle pathology and muscle function of Tg/mdx were confirmed. On the other hand, nNOS of Tg/mdx exists as an activated form and its localization was changed from sarcolemma to cytosol. We found that activated nNOS in Tg/mdx led to hyper-nitrosylation of the RyR1 and subsequent constant Ca2+ release from SR to cytosol. These phenomena were also confirmed in mdx. However, the function of RyR1 stimulated by caffeine and SERCA were maintained in Tg/mdx and wild type but not in mdx.
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