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Elucidation of the novel functions of EXTL3 involved in the biosynthesis of heparan sulfate in brains and T cells

Research Project

Project/Area Number 18K06670
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research InstitutionMeijo University

Principal Investigator

Yamada Shuhei  名城大学, 薬学部, 教授 (70240017)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsヘパラン硫酸 / EXTL3 / ノックアウトマウス / 脳 / T細胞 / へパラン硫酸 / グリコサミノグリカン / 糖転移酵素
Outline of Final Research Achievements

The aim of this study is elucidation of the biological roles of EXTL3, a biosynthetic enzyme of heparan sulfate. Brain glutamatergic nerve-specific Extl3-deficient mice were successfully generated and their behavioral as well as physical phenotypes were investigated. So far, typical abnormalities have not been observed. It may be involved in the higher functions in brain. Other enzymes may compensate the enzymatic activity of Extl3. T cell-specific Extl3-deficient mice were also successfully generated. Using the spleenish cells, differentiation of T cells was examined, and it turned out to tend to be immature. Cells of a patient with mutation in EXTL3 were cultured and the amount as well as the disaccharide compositions of glycosaminoglycans from them were examined. Heparan sulfate from the patient was reduced compared with that from a healthy subject.

Academic Significance and Societal Importance of the Research Achievements

ヘパラン硫酸は生体内に普遍的に存在し、細胞の増殖や分化など、非常に基本的な機能に関わっている。ヘパラン硫酸を欠損すると致死となるため、極めて重要な分子である。したがって、ヘパラン硫酸の各臓器における役割の解明は、科学の発展に大いに貢献することができるため、本研究の学術的な意義は極めて大きい。また、EXTL3を欠損した遺伝病の患者の報告例はまだ少ないが、今後さらに見つかってくることが予想される。本研究は、そのような難治性の希少疾患の発症メカニズムの解明や治療法の開発につながる可能性があり、社会的意義は大きい。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (18 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (4 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (11 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Remarks (2 results)

  • [Int'l Joint Research] Marmara大学(トルコ)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Congenital Disorders Caused by Defects in Catabolism of Glycosaminoglycans2020

    • Author(s)
      Shuhei Yamada, Shuji Mizumoto
    • Journal Title

      Trends in Glycoscience and Glycotechnology

      Volume: 32 Issue: 188 Pages: E127-E133

    • DOI

      10.4052/tigg.1968.1E

    • NAID

      130007879857

    • ISSN
      0915-7352, 1883-2113
    • Year and Date
      2020-07-25
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Congenital Disorders Caused by Defects in Anabolism of Glycosaminoglycans2020

    • Author(s)
      Shuji Mizumoto, Shuhei Yamada
    • Journal Title

      Trends in Glycoscience and Glycotechnology

      Volume: 32 Issue: 186 Pages: E45-E51

    • DOI

      10.4052/tigg.1759.1E

    • NAID

      130007815517

    • ISSN
      0915-7352, 1883-2113
    • Year and Date
      2020-03-25
    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Specific functions of Exostosin-like 3 (EXTL3) gene products2020

    • Author(s)
      Shuhei Yamada
    • Journal Title

      Cellular & Molecular Biology Letters

      Volume: 25 Issue: 1 Pages: 39-39

    • DOI

      10.1186/s11658-020-00231-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Importance of the Fine Structure of Glycolsaminoglycans2019

    • Author(s)
      Shuhei Yamada
    • Journal Title

      Trends in Glycoscience and Glycotechnology

      Volume: 31

    • NAID

      130007683624

    • Related Report
      2019 Research-status Report
  • [Presentation] Cre/LoxPシステムを利用したT細胞特異的Extl3欠損マウスの作製とその解析2021

    • Author(s)
      大橋里帆、水本秀二、山下匡、菅原明、山田修平
    • Organizer
      糖鎖科学中部拠点 第16回若手の力 フォーラム
    • Related Report
      2020 Annual Research Report
  • [Presentation] 免疫細胞(T細胞)特異的EXTL3欠損マウスの解析2020

    • Author(s)
      樋口直美、三宅晃代、水本秀二、山下匡、菅原明、山田修平
    • Organizer
      第52回日本結合組織学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Congenital disorders caused by defects in biosynthesis of glycosaminoglycans2020

    • Author(s)
      Shuhei Yamada
    • Organizer
      Pan Pacific Connective Tissue Societies Symposium 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 脳のグルタミン酸作動性神経特異的 EXTL3 欠損マウスの解析2019

    • Author(s)
      山田夏実,水本秀二,衣斐大祐,菅原明,山田 修平
    • Organizer
      第38回日本糖質学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 免疫細胞(T 細胞)特異的 EXTL3 欠損マウスの解析2019

    • Author(s)
      三宅晃代、水本秀二、山下匡、菅原明、山田修平
    • Organizer
      第38回日本糖質学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 脊椎骨端骨幹端異形成症患者のリンパ芽球様細胞株の産生するヘパラン硫酸の解析2019

    • Author(s)
      佐藤亨、水本秀二、大橋博文、逆井悦子、Nursel H Elcioglu、 三宅紀子 、松本直通、池川 志郎、山田 修平
    • Organizer
      第38回日本糖質学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Analysis of heparan sulfate produced by lymphoblastoid cell lines in patients with spondylo-epi-metaphyseal dysplasia2019

    • Author(s)
      Toru Sato, Shuji Mizumoto, Hirofumi Ohashi, Etsuko Sakasai, Nursel H Elcioglu, Noriko Miyake, Naomichi Matsumoto, Shiro Ikegawa, Shuhei Yamada
    • Organizer
      11th international Conference on Proteoglyans
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヘパラン硫酸生合成酵素であるEXTL3の変異は免疫異常を伴う新たなタイプの脊椎骨端骨幹端異形成症を引き起こす2018

    • Author(s)
      Long Guo, Nursel H Elcioglu, Shuji Mizumoto, Zheng Wang, Bilge Noyan, Hatice M Albayrak, Shuhei Yamada, Naomichi Matsumoto, Noriko Miyake, Gen Nishimura, Shiro Ikegawa
    • Organizer
      日本生化学会中部支部第82回例会・シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] リンパ芽球様細胞株の産生するグリコサミノグリカンの解析2018

    • Author(s)
      篠田はるか、持永磨奈美、伊藤有沙、水本秀二、逆井悦子、大橋博文、山田修平
    • Organizer
      第64回日本薬学会東海支部 総会・大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Structural studies on heparan sulfate produced by the lymphoblastoid cell lines prepared from a patient with a mutation in EXTL3 and embryonic cells from Extl3-deficient mice2018

    • Author(s)
      Shuhei Yamada, Shuji Mizumoto, Hirofumi Ohashi, Etsuko Sakasai, Nursel H Elcioglu, Noriko Miyake, Naomichi Matsumoto, Daisuke Ibi, Akira Sugawara, Shiro Ikegawa
    • Organizer
      Gordon Research Conference on Proteoglycans 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 免疫異常を伴う脊椎骨端骨幹端異形成症はヘパラン硫酸の生合成を担うEXTL3の変異により引き起こされる2018

    • Author(s)
      水本秀二、Long Guo, Nursel H Elcioglu, Zheng Wang, Bilge Noyan, Hatice M Albayrak, 松本直通、三宅紀子、西村 玄、山田修平、池川志郎
    • Organizer
      第37回日本糖質学会年会
    • Related Report
      2018 Research-status Report
  • [Remarks] 名城大学薬学部病態生化学研究室ホームページ

    • URL

      http://www-yaku.meijo-u.ac.jp/Research/Laboratory/pathobio/index.html

    • Related Report
      2020 Annual Research Report 2018 Research-status Report
  • [Remarks] 名城大学病態生化学研究室

    • URL

      http://www-yaku.meijo-u.ac.jp/Research/Laboratory/pathobio/index.html

    • Related Report
      2019 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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