Elucidation of pathogenesis of muscular dystrophies caused by constitutive extracellular calcium influx
| Project/Area Number |
15H04846
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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 Center of Neurology and Psychiatry |
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Principal Investigator |
Noguchi Satoru 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第一部, 室長 (00370982)
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| Co-Investigator(Kenkyū-buntansha) |
原 雄二 京都大学, 工学(系)研究科(研究院), 助手 (60362456)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2017: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2015: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| Keywords | 遺伝性疾患 / ミオパチー / カルシウム / 病態 / モデルマウス / チャンネル / 遺伝病 / 骨格筋 / 糖鎖 |
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| Outline of Final Research Achievements |
We identified two dominant mutations in ORAI1 gene in tubular myopathy patients. The patients’ cells and the cells expressing the mutated ORAI1 showed constitutive activation of ORAI1 channels showing extracellular calcium entry dependent on extracellular calcium concentration.
We chronologically analyzed the muscle pathology of mouse model with a dominant ORAI1 mutation. The muscle phenotypes were quite milder, nevertheless they showed necrosis and regeneration.We produced new mouse model with a dominant STIM1 mutation. These mice revealed small body weight and had atrophic muscles. On muscle pathology, severe phenotypes were observed showing remarkable dystrophic changes, necrosis and centrally-placed fibers as well as enhanced fibrosis and ectopic adipose tissue replacement.
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Tubular aggregate myopathy caused by a novel mutation in the cytoplasmic domain of STIM12016
Author(s)
Oakum H, Saito F, Jun Mitsui J, Hara Y, Hatanaka Y, Ikeda M, Shimizu T, Matsumura K, Shimizu J, Tsui S, Sonoo M.
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Journal Title
Neurol Genet
Volume: 2:e50
Issue: 1
Pages: 50-50
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Development of a Novel Tetravalent Synthetic Peptide That Binds to Phosphatidic Acid.2015
Author(s)
Rina Ogawa, Kohjiro Nagao, Kentaro Taniuchi, Masaki Tsuchiya, Utako Kato, Yuji Hara, Takehiko Inaba, Toshihide Kobayashi, Yoshihiro Sasaki, Kazunari Akiyoshi, Miho Watanabe-Takahashi, Kiyotaka Nishikawa, Masato Umeda
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Journal Title
PLOS ONE
Volume: 10
Issue: 7
Pages: e0131668-e0131668
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Presentation] Tubular aggregate myopathy with dystrophic features2017
Author(s)
Lee J, Yoshimura M, Hirano R, Miyatake W, Koshimizu E, Matsumoto N, Mori H, Tachii N, Suzuki M, Ogata K, Nishino I, Noguchi S
Organizer
22nd International Congress of the World Muscle Society
Related Report
Int'l Joint Research
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