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The production of newly ALS model mice

Research Project

Project/Area Number 24591275
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionKitasato University

Principal Investigator

NAGAI MAKIKO  北里大学, 医学部, 講師 (80420488)

Research Collaborator NIHIRA Tomoko  
KAWANAMI Aya  
Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords筋萎縮性側索硬化症 / TDP-43 / アデノ随伴ウィルス / マウスモデル / 脊髄前角細胞 / トランスジェニックマウス / アデノ随伴ウイルス / 動物モデル / optineurin / TDP-43 / Thy-1プロモーター / 神経変性 / 脊髄 / 運動神経 / Thy-1 / VachT-Cre
Outline of Final Research Achievements

TDP-43 was identified as the major protein component of the aggregations in the affected neurons of amyotrophic lateral sclerosis (ALS) patients.We generated the transgenic mice with loxP-dsRed-loxP-TDP-43 under the control of Thy-1.This mouse expressed dsRed in neurons of brain and spinal cord.Then we crossed this mouse with VAcht-Cre mouse, which expressed Cre in motor neurons. We expected the motor neuron deaths in the spinal cords of these double transgenic mice to use as the ALS model. These double transgenic mice did not expressed the paralysis, because the insufficiency of TDP-43 protein level.
We used adeno-associated virus (AAV) vectors to overexpress the TDP-43 in the mice motor neurons. TDP-43-WT and TDP-43-A315T mice showed muscle weakness of the left hindlimb from 2 weeks of injection. We may use these mice as ALS model.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (13 results)

All 2015 2014 2013 2012 Other

All Journal Article (4 results) (of which Acknowledgement Compliant: 1 results,  Peer Reviewed: 2 results) Presentation (9 results)

  • [Journal Article] Clinicopathological examination of optineurin-immunoreactive inclusions in patients with sporadic ALS2015

    • Author(s)
      Kawanami A, Nagai M, Nihiira T, Ogino M, Nishiyama K.
    • Journal Title

      The Kitasato Medical Journal

      Volume: 45 Pages: 21-28

    • NAID

      40020413545

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Acknowledgement Compliant
  • [Journal Article] Loss of DARPP-32 and calbindin in multiple system atrophy2013

    • Author(s)
      Hayakawa H, Nagai M, Kawanami A, Nakata Y, Nihira T, Ogino M, Takada M, Saido T, Takano J, Saegusa M, Mikami T, Hamada J, Nishiyama K, Mochizuki H, Mizuno Y
    • Journal Title

      Journal of Neural Transmission

      Volume: 120 Issue: 12 Pages: 1689-1698

    • DOI

      10.1007/s00702-013-1039-4

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 筋萎縮性側索硬化症の病態解明と治療戦略2012

    • Author(s)
      永井真貴子,西山和利
    • Journal Title

      北里医学

      Volume: 42(2) Pages: 85-93

    • NAID

      40019551506

    • Related Report
      2012 Research-status Report
  • [Journal Article] Accumulation of a-synuclein triggered by presynaptic dysfunction2012

    • Author(s)
      Nakata Y, Yasuda T, Fukaya M, Yamamori S, Itakura M, Nihira T, Hayakawa H, Kawanami A, Kataoka M, Nagai M, Sakagami H, Takahashi M, Mizuno Y, Mochizuki H
    • Journal Title

      J. Neurosci

      Volume: 32 Issue: 48 Pages: 17186-17196

    • DOI

      10.1523/jneurosci.2220-12.2012

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 認知症を伴う筋萎縮性側索硬化症の臨床・病理学的評価2015

    • Author(s)
      永井真貴子,川浪文,近藤裕子,西山和利
    • Organizer
      第34回日本認知症学会学術集会
    • Place of Presentation
      リンクステーションホテル(青森市)
    • Year and Date
      2015-10-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] 認知症を伴った筋萎縮性側索硬化症剖検脳の免疫組織学的検討2015

    • Author(s)
      永井真貴子,川浪文、荻野美恵子、西山和利
    • Organizer
      第56回日本神経学会学術大会
    • Place of Presentation
      朱鷺メッセ(新潟市)
    • Year and Date
      2015-05-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] C-terminal fragment of TDP-43 induce chronic motor neuron degeneration in mouse spinal cord2014

    • Author(s)
      Nagai M, Kawanami A, Nihira T, Nishiyama K.
    • Organizer
      9th FENS Forum of Neuroscience
    • Place of Presentation
      ミラノ(イタリア)
    • Year and Date
      2014-07-05 – 2014-07-09
    • Related Report
      2014 Research-status Report
  • [Presentation] TDP-43のC末端断片発現ALSモデルマウスの作製2014

    • Author(s)
      永井真貴子,川浪文、仁平友子、西山和利
    • Organizer
      第55回日本神経学会学術大会
    • Place of Presentation
      福岡国際会議場(福岡県・福岡市)
    • Year and Date
      2014-05-21 – 2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] 孤発性ALS剖検脊髄におけるOptineurin陽性封入体の検討2014

    • Author(s)
      川浪文,永井真貴子,仁平友子,荻野美恵子,西山和利
    • Organizer
      第55回日本神経学会学術大会
    • Place of Presentation
      福岡国際会議場(福岡県・福岡市)
    • Year and Date
      2014-05-21 – 2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] Mutant TDP-43 overexpression produces the motor neuron cell death in mouse spinal cord.2012

    • Author(s)
      Nagai M, Kawanami A, NihiraT, Hayakawa H, Nakata Y, Mizuno Y, Mochizuki H
    • Organizer
      8th FENS Forum of Neuroscience
    • Place of Presentation
      Barcelona, Spain
    • Related Report
      2012 Research-status Report
  • [Presentation] TDP43発現ALSマウスモデルの作製2012

    • Author(s)
      永井真貴子,川浪文,早川英規,仁平友子,望月秀樹
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] TDP-43のC末端断片発現ALSモデルマウスの作成

    • Author(s)
      永井真貴子,川浪文,仁平友子,早川英規,水野美邦,西山和利
    • Organizer
      第54回日本神経学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] C-terminal fragment of TDP-43 induce chronic motor neuron degeneration in mouse spinal cord

    • Author(s)
      Nagai M, Kawanami A, Nihira T, Nishiyama K, Mizuno Y.
    • Organizer
      Neuroscience 2013
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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