Elucidation of molecular architecture of neuromuscular junction and dissection of molecular pathomechanisms of congenital myasthenic syndromes
Project/Area Number |
15H04840
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
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Research Institution | Nagoya University |
Principal Investigator |
Ohno Kinji 名古屋大学, 医学系研究科, 教授 (80397455)
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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 |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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Keywords | 先天性筋無力症候群 / アセチルコリン受容体 / Rspo2 / GFPT1 / iPS細胞 / 神経筋接合部 / RSPO2 / DOK7 / LGR5 / agrin |
Outline of Final Research Achievements |
Laser capture microdissection of the mouse spinal motor neurons (SMN) revealed that Rspo2 is highly expressed in spinal motor neurons. Rspo2 induces acetylcholine receptor (AChR) clustering, which is ~80% as potent as agrin. Tissue-specific rescue of Rspo2 by transgenic expression of Rspo2 by SMN- and muscle-specific promoters revealed that SMN-derived Rspo2 plays essential roles in the formation of the neuromuscular junction and AChR clustering. We propose that Rspo2 is an essential AChR clustering-inducing molecule after agrin. We started dissection of molecular pathomechanisms of mutations in a gene encoding glycosylation enzyme, GFPT1, which were identified in Japanese patients with congenital myasthenic syndrome.
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Report
(4 results)
Research Products
(52 results)
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[Journal Article] Loss of Sfpq causes long-gene transcriptopathy in the brain2018
Author(s)
Takeuchi A, Iida K, Tsubota T, Hosokawa M, Denawa M, Ninomiya K, Ito M, Kimura H, Abe T, Kiyonari H, Ohno K, Hagiwara M.
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Journal Title
NAID
Related Report
Peer Reviewed
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[Journal Article] An ENU-induced splice site mutation of mouse Col1a1 causing recessive osteogenesis imperfecta and revealing a novel splicing rescue.2017
Author(s)
Tabeta K, Du X, Arimatsu K, Yokoji M, Takahashi N, Amizuka N, Hasegawa T, Crozat K, Maekawa T, Miyauchi S, Matsuda Y, Ida T, Kaku M, Hoebe K, Ohno K, Yoshie H, Yamazaki K, Moresco EMY, Beutler B
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Journal Title
Sci. Rep.
Volume: 7(1)
Issue: 1
Pages: 11717-11717
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] R-spondin 2 promotes acetylcholine receptor clustering at the neuromuscular junction via Lgr5.2016
Author(s)
Nakashima H., Ohkawara B., Ishigaki S., Fukudome T., Ito K., Tsushima M., Konishi H., Okuno T., Yoshimura T., Ito M., Masuda A., Sobue G., Kiyama H., Ishiguro N., Ohno K.
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Journal Title
Sci Rep
Volume: 22
Issue: 1
Pages: 28512-28512
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A missense mutation in domain III in HSPG2 in Schwartz-Jampel syndrome compromises secretion of perlecan into the extracellular space.2015
Author(s)
Iwata S, Ito M, Nakata T, Noguchi Y, Okuno T, Ohkawara B, Masuda A, Goto T, Adachi M, Osaka H, Nonaka R, Arikawa-Hirasawa E, Ohno K.
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Journal Title
Neuromuscul Disord.
Volume: 25(8)
Issue: 8
Pages: 667-71
DOI
Related Report
Peer Reviewed
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[Journal Article] Collagen Q and anti-MuSK autoantibody competitively suppress agrin/LRP4/MuSK signaling.2015
Author(s)
Otsuka K, Ito M, Ohkawara B, Masuda A, Kawakami Y, Sahashi K, Nishida H, Mabuchi N, Takano A, Engel AG, Ohno K.
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Journal Title
Sci Rep.
Volume: 5
Issue: 1
Pages: 13928-13928
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] LRP4 third β-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated MuSK signaling in a position-specific manner2014
Author(s)
Ohkawara B, Cabrera-Serrano M, Nakata T, Milone M, Asai N, Ito K, Ito M, Masuda A, Ito Y, Engel AG, Ohno K
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Journal Title
Hum Mol Genet.
Volume: Apr 1;23(7)
Issue: 7
Pages: 1856-68
DOI
Related Report
Peer Reviewed / Open Access
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