Protein-anchoring therapy for mdx mouse model of duchenne muscular dystrophy
Project/Area Number |
25430049
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Nerve anatomy/Neuropathology
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Research Institution | Nagoya University |
Principal Investigator |
Ito Mikako 名古屋大学, 医学系研究科, 助教 (60444402)
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Project Period (FY) |
2013-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | 筋ジストロフィー / AAV / Biglycan / mdx / デュシャンヌ型筋ジストロフィー / デュシャンヌ型筋ジストロ フィー / biglycan / 遺伝子治療 |
Outline of Final Research Achievements |
Duchenne muscular dystrophy (DMD) is a devastating muscle disease caused by loss-of-function mutationsin DMD encoding dystrophin. Utrophin is a paralog ofdystrophin and is highly expressed at the neuromuscular junction. In mdx mice, utrophin is naturally upregulated throughout the muscle fibers, which mitigates muscular dystrophy. The protein-anchoring therapy was applied to mdx mice in this study. rAAV8 carrying hBGN encoding human biglycan was intravenously injected into 5-week-old mdx mice. The rAAV8-hBGN treatment improved motor deficits and decreased plasma creatine kinase activities. In muscle sections of treated mice, the number of central myonuclei and the distribution of myofiber sizes were improved. The low transduction efficiency and improved motor functions suggest that biglycan expressed in a small number of muscle fibers was likely to have been secreted and anchored to the cell surface throughout the whole muscular fibers.
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Report
(5 results)
Research Products
(35 results)
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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] Congenital myasthenic syndrome in Japan: ethnically unique mutations in muscle nicotinic acetylcholine receptor subunits2015
Author(s)
Azuma Y, Nakata T, Tanaka M, Shen XM, Ito M, Iwata S, Okuno T, Nomura Y, Ando N, Ishigaki K, Ohkawara B, Masuda A, Natsume J, Kojima S, Sokabe M, Ohno K.
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Journal Title
Neuromuscul Disord
Volume: 25(1)
Issue: 1
Pages: 60-69
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Searching for genomic region of high-fat diet-induced type 2 diabetes in mouse chromosome 2 by analysis of congenic strains2014
Author(s)
4.Kobayashi M, Ohno T, Ihara K, Murai, A., Kumazawa, M., Hoshino, H., Iwanaga, K., Iwai, H., Hamana, Y., Ito, M., Ohno, K., Horio, M..
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Journal Title
Plos One
Volume: 9
Issue: 5
Pages: e96271-e96271
DOI
Related Report
Peer Reviewed / Open Access
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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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[Journal Article] Verapamil protects against cartilage degradation in osteoarthritis by inhibiting Wnt/β-catenin signaling.2014
Author(s)
Takamatsu, A., Ohkawara, B., Ito, M., Masuda, A., Sakai, T., Ishiguro, N. and Ohno, K.
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Journal Title
PLOS ONE
Volume: 9(3)
Issue: 3
Pages: e92699-e92699
DOI
Related Report
Peer Reviewed / Open Access
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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, A. G. and Ohno, K
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Journal Title
Hum. Mol. Genet.
Volume: in press
Related Report
Peer Reviewed
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[Journal Article] Maternal molecular hydrogen administration ameliorates rat fetal hippocampal damage by in utero ischemia-reperfusion2014
Author(s)
Mano, Y., Kotani, T., Ito, M., Nagai, T., Ichinohashi, Y., Yamada, K., Ohno, K., Kikkawa, F. and Toyokuni, S.
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Journal Title
Free Radic. Biol. Med.
Volume: in press
Related Report
Peer Reviewed
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[Journal Article] Meclozine facilitates proliferation and differentiation of chondrocytes by attenuating abnormally activated FGFR3 signaling in achondroplasia.2013
Author(s)
Matsushita, M., Kitoh, H., Ohkawara, B., Mishima, K., Kaneko, H., Ito, M., Masuda, A., Ishiguro, N. and Ohno, K.
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Journal Title
PLOS ONE
Volume: 8(12)
Issue: 12
Pages: 81569-81569
DOI
Related Report
Peer Reviewed
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[Journal Article] HnRNP L and hnRNP LL antagonistically modulate PTB-mediated splicing suppression of CHRNA1 pre-mRNA.2013
Author(s)
Rahman, M. A., Masuda, A., Ohe, K., Ito, M. , Hutchinson, D. O., Mayeda, A., Engel, A. G. and Ohno, K.
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Journal Title
Sci. Rep.
Volume: 3
Issue: 1
Pages: 2931-2931
DOI
Related Report
Peer Reviewed
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[Journal Article] Mutations in the C-Terminal Domain of ColQ in Endplate Acetylcholinesterase Deficiency Compromise ColQ-MuSK Interaction.2013
Author(s)
Nakata T, Ito M, Azuma Y, Otsuka K, Noguchi Y, Komaki H, Okumura A, Shiraishi K, Masuda A, Natsume J, Kojima S, Ohno K.
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Journal Title
Human Mutation
Volume: in press
Issue: 7
Pages: 997-1004
DOI
Related Report
Peer Reviewed
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