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Protein-anchoring therapy for mdx mouse model of duchenne muscular dystrophy

Research Project

Project/Area Number 25430049
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Nerve anatomy/Neuropathology
Research InstitutionNagoya University

Principal Investigator

Ito Mikako  名古屋大学, 医学系研究科, 助教 (60444402)

Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
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.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (35 results)

All 2017 2016 2015 2014 2013 Other

All Journal Article (29 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 29 results,  Open Access: 16 results,  Acknowledgement Compliant: 11 results) Presentation (3 results) Remarks (3 results)

  • [Journal Article] Protein-anchoring therapy of biglycan for mdx mouse model of Duchenne muscular dystrophy2017

    • Author(s)
      Ito M*, Ehara Y*, Li J, Inada K, Ohno K. *Equal contribution.
    • Journal Title

      Hum Gene Ther

      Volume: - Issue: 5 Pages: 428-436

    • DOI

      10.1089/hum.2015.088

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Competitive regulation of alternative splicing and alternative polyadenylation by hnRNP H and CstF64 determines acetylcholinesterase isoforms2017

    • Author(s)
      Nazim M, Masuda A, Rahman MA, Nasrin F, Takeda JI, Ohe K, Ohkawara B, Ito M, Ohno K.
    • Journal Title

      Nucleic Acids Res

      Volume: - Pages: 1455-1468

    • DOI

      10.1093/nar/gkw823

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] R-spondin 2 facilitates differentiation of proliferating chondrocytes into hypertrophic chondrocytes by enhancing Wnt/β-catenin signaling in endochondral ossification.2016

    • Author(s)
      Takegami Y, Ohkawara B, Ito M, Masuda A, Nakashima H, Ishiguro N, Ohno K.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: S0006-291X(16) Issue: 1 Pages: 30400-4

    • DOI

      10.1016/j.bbrc.2016.03.089

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Roles of collagen Q in MuSK antibody-positive myasthenia gravis2016

    • Author(s)
      Ohno K, Ito M, Otsuka K
    • Journal Title

      Chem Biol Interact

      Volume: 259 Pages: 266-270

    • DOI

      10.1016/j.cbi.2016.04.019

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [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.
    • Journal Title

      Sci Rep

      Volume: 22 Issue: 1 Pages: 28512-28512

    • DOI

      10.1038/srep28512

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular hydrogen suppresses activated Wnt-catenin signaling.2016

    • Author(s)
      Y. Lin, B. Ohkawara, M. Ito, N. Misawa, K. Miyamoto, Y. Takegami, A. Masuda, S. Toyokuni, K Ohno
    • Journal Title

      Scientific Report

      Volume: 25 Issue: 1 Pages: 31986-31986

    • DOI

      10.1038/srep31986

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular hydrogen alleviates motor deficits and muscle degeneration in mdx mice2016

    • Author(s)
      Hasegawa S, Ito M, Fukami M, Hashimoto M, Hirayama M, Ohno K
    • Journal Title

      Redox Report

      Volume: in press

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Hydrogen-rich water ameliorates bronchopulmonary dysplasia (BPD) in newborn rats.2016

    • Author(s)
      Muramatsu Y, Ito M, Oshima T, Kojima S, Ohno K
    • Journal Title

      Pediatr Pulmonol.

      Volume: in press Issue: 9 Pages: 928-935

    • DOI

      10.1002/ppul.23386

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Simultaneous oral and inhalational intake of molecular hydrogen additively suppresses signaling pathways in rodents.2015

    • Author(s)
      Sobue S, Yamai K, Ito M, Ohno K, Ito M, Iwamoto T, Qiao S, Ohkuwa T, Ichihara M
    • Journal Title

      Mol Cell Biochem.

      Volume: 403 Issue: 1-2 Pages: 231-241

    • DOI

      10.1007/s11010-015-2353-y

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Dopaminergic neuron-like stem cells from human deciduous teeth promote neurological recovery in Parkinsonian rats by cell replacement and paracrine neuroregenerative mechanisms2015

    • Author(s)
      Hiromi Fujii, Kohki Matsubara, Kiyoshi Sakai, Mikako Ito, Kinji Ohno, Minoru Ueda, Akihito Yamamoto
    • Journal Title

      Brain Research

      Volume: 1613 Pages: 5972-5972

    • DOI

      10.1016/j.brainres.2015.04.001

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Position-specific binding of FUS to nascent RNA regulates mRNA length.2015

    • Author(s)
      Masuda A, Takeda J, Okuno T, Okamoto T, Ohkawara B, Ito M, Ishigaki S, Sobue G, Ohno K.
    • Journal Title

      Genes Dev.

      Volume: 29(10) Issue: 10 Pages: 1045-57

    • DOI

      10.1101/gad.255737.114

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hydrogen ameliorates pulmonary hypertension in rats by anti-inflammatory and anti-oxidant effects.2015

    • Author(s)
      Kishimoto Y, Kato T, Ito M, Azuma Y, Fukasawa Y, Ohno K, Kojima S.
    • Journal Title

      J Thorac Cardiovasc Surg.

      Volume: 150 Issue: 3 Pages: 645654-645654

    • DOI

      10.1016/j.jtcvs.2015.05.052

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [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.
    • Journal Title

      Neuromuscul Disord.

      Volume: 25(8) Issue: 8 Pages: 667-71

    • DOI

      10.1016/j.nmd.2015.05.002

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [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.
    • Journal Title

      Sci Rep.

      Volume: 5 Issue: 1 Pages: 13928-13928

    • DOI

      10.1038/srep13928

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles.2015

    • Author(s)
      Ichihara M, Sobue S, Ito M, Ito M, Hirayama M, Ohno K.
    • Journal Title

      Med Gas Res

      Volume: 5 Issue: 1 Pages: 12-12

    • DOI

      10.1186/s13618-015-0035-1

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Lansoprazole upregulates polyubiquitination of TRAF6 and facilitates Runx2-mediated osteoblastogenesis2015

    • Author(s)
      Kenichi Mishima, Hiroshi Kitoh, Bisei Ohkawara, Tatsuya Okuno, Mikako Ito, Akio Masuda, Naoki Ishiguro, Kinji Ohno
    • Journal Title

      EBio Medicin

      Volume: 2 Issue: 12 Pages: 20462061-20462061

    • DOI

      10.1016/j.ebiom.2015.11.024

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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.
    • Journal Title

      Neuromuscul Disord

      Volume: 25(1) Issue: 1 Pages: 60-69

    • DOI

      10.1016/j.nmd.2014.09.002

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] LRP4 induces extracellular matrix productions and facilitates chondrocyte differentiation2014

    • Author(s)
      Asai N, Ohkawara B, Ito M, Masuda A, Ishiguro N, Ohno K
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 451 Issue: 2 Pages: 302-307

    • DOI

      10.1016/j.bbrc.2014.07.125

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [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..
    • Journal Title

      Plos One

      Volume: 9 Issue: 5 Pages: e96271-e96271

    • DOI

      10.1371/journal.pone.0096271

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [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
    • Journal Title

      Hum Mol Genet.

      Volume: Apr 1;23(7) Issue: 7 Pages: 1856-68

    • DOI

      10.1093/hmg/ddt578

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maternal molecular hydrogen administration ameliorates rat fetal hippocampal damage by in utero ischemia-reperfusion.2014

    • Author(s)
      Mano Y, Kotani T, Ito M, Nagai T, Ichinohashi Y, Yamada K, Ohno K, Kikkawa F, Toyokuni S.
    • Journal Title

      Free Radic Biol Med.

      Volume: 69 Pages: 324-330

    • DOI

      10.1016/j.freeradbiomed.2014.01.037

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [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.
    • Journal Title

      PLOS ONE

      Volume: 9(3) Issue: 3 Pages: e92699-e92699

    • DOI

      10.1371/journal.pone.0092699

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [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
    • Journal Title

      Hum. Mol. Genet.

      Volume: in press

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [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.
    • Journal Title

      Free Radic. Biol. Med.

      Volume: in press

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Collagen Q is a key player for developing rational therapy for congenital myasthenia and for dissecting the mechanisms of anti-MuSK myasthenia gravis2014

    • Author(s)
      Ohno, K. and Ito, M. and Kawakami, Y
    • Journal Title

      J. Mol. Neurosci.

      Volume: in press

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [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.
    • Journal Title

      PLOS ONE

      Volume: 8(12) Issue: 12 Pages: 81569-81569

    • DOI

      10.1371/journal.pone.0081569

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [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.
    • Journal Title

      Sci. Rep.

      Volume: 3 Issue: 1 Pages: 2931-2931

    • DOI

      10.1038/srep02931

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [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.
    • Journal Title

      Human Mutation

      Volume: in press Issue: 7 Pages: 997-1004

    • DOI

      10.1002/humu.22325

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular hydrogen attenuates fatty acid uptake and lipid accumulation through downregulating CD36 expression in HepG2 cells2013

    • Author(s)
      Iio A, Ito M, Itoh T, Terazawa R, Fujita Y, Nozawa Y, Ohsawa I, Ohno K, Ito M
    • Journal Title

      Med Gas Res

      Volume: 3 Issue: 1 Pages: 6-6

    • DOI

      10.1186/2045-9912-3-6

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] デュシャンヌ型筋ジストロフィーmdxマウスにおけるbiglycanタンパク係留療法2016

    • Author(s)
      伊藤美佳子、江原佑佳、李 晋、稲田亘佑、大野欽司
    • Organizer
      第39回分子生物学会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Schwartz-Jampel 症候群を引き起こすHSPG2 (パールカン)の遺伝子変異2015

    • Author(s)
      伊藤 美佳子、岩田 哲、中田 智彦、野口 陽一朗、奥野 達矢、大河原美静、増田章男、後藤知英、安達昌功、小坂 仁、野中 里 紗、平澤 恵理、大野 欽司
    • Organizer
      第1回日本筋学会
    • Place of Presentation
      NCNP 東京都 小平市
    • Year and Date
      2015-08-08
    • Related Report
      2015 Research-status Report
  • [Presentation] 分子状水素は糖代謝変化を誘導する2015

    • Author(s)
      伊藤 美佳子、曽我 朋義、大野 欽司
    • Organizer
      第5回分子状水素医学シンポジウム
    • Place of Presentation
      ウィンクあいち 愛知県名古屋市
    • Year and Date
      2015-03-21
    • Related Report
      2014 Research-status Report
  • [Remarks] 名古屋大学 大学院医学系研究科 神経遺伝情報学

    • URL

      https://www.med.nagoya-u.ac.jp/neurogenetics/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 名古屋大学医学系研究科 神経遺伝情報学

    • URL

      http://www.med.nagoya-u.ac.jp/neurogenetics/

    • Related Report
      2015 Research-status Report 2014 Research-status Report
  • [Remarks] 名古屋大学医学系研究科 先端応用医学部門 神経遺伝情報学

    • URL

      http://www.med.nagoya-u.ac.jp/neurogenetics/

    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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