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Loss of hematopoietic mucin-type O-glycan causes thrombocytopenia in mice

Research Project

Project/Area Number 24300152
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Laboratory animal science
Research InstitutionUniversity of Tsukuba

Principal Investigator

KUDO Takashi  筑波大学, 医学医療系, 准教授 (20288062)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Satoru  筑波大学, 医学医療系, 教授 (50271896)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2012: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Keywords動物 / 糖鎖 / 発生・分化 / 血小板 / 発生分化
Outline of Final Research Achievements

Mucin function has been difficult to characterize because its structure and synthesis are complex. To address the biological role of mucin-type O-glycans in hematopoietic cells, we conditionally ablated C1galt, which is essential for synthesis of mucin-type O-glycans. Inducible, Mx1-cre-mediated C1galt conditional knockout (Mx1-C1) mice exhibited severe thrombocytopenia, giant platelets, and prolonged bleeding times.There were few proplatelets in cultured Mx1-C1 primary megakaryocytes. Moreover, the expression of hypoglycosylated GpIbα protein in Mx1-C1 megakaryocytes and platelets was greatly reduced despite the fact that expression of gpIbα transcript was unchanged. Our observations indicate that O-glycan is required for terminal megakaryocyte differentiation and platelet production and that the decrease in GpIbα in cells lacking O-glycan may be caused by increased proteolysis.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (6 results)

All 2014 2013 Other

All Journal Article (3 results) (of which Acknowledgement Compliant: 1 results,  Peer Reviewed: 1 results) Presentation (2 results) (of which Invited: 1 results) Book (1 results)

  • [Journal Article] 血小板減少症を呈するムチンO-結合型糖鎖欠損マウスの解析2014

    • Author(s)
      工藤 崇、高橋 智
    • Journal Title

      医学のあゆみ

      Volume: 249 Pages: 688-692

    • Related Report
      2014 Annual Research Report
    • Acknowledgement Compliant
  • [Journal Article] 巨核球分化におけるムチン型糖鎖修飾の意義2014

    • Author(s)
      工藤 崇、高橋 智
    • Journal Title

      血液内科

      Volume: 68 Pages: 698-703

    • NAID

      40020114866

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Clgalt1-deficient mice exhibit thrombocytopenia due to abnormal terminal differentiation of megakaryocytes2013

    • Author(s)
      Kudo T, et al. (13人中8番目)
    • Journal Title

      Blood

      Volume: 122 Issue: 9 Pages: 1649-1657

    • DOI

      10.1182/blood-2012-12-471102

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Loss of hematopoietic mucin-type O-glycan causes thrombocytopenia in mice2014

    • Author(s)
      工藤 崇
    • Organizer
      第36回日本血栓止血学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-05-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] C1galt1欠損マウスは巨核球の最終分化異常による血小板減少症をおこす

    • Author(s)
      工藤 崇、佐藤 隆、萩原 梢、上妻 行則、山口高志、池原 譲、濱田理人、松本 健、依馬正次、村田聡一郎、大河内信弘、成松 久、高橋 智
    • Organizer
      第36日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2013 Annual Research Report
  • [Book] Glycoscience: Biology and Medicine.'Role of mucin-type O-glycan in megakaryocyte differentiation'2014

    • Author(s)
      Takashi Kudo, Satoru Tkahashi
    • Total Pages
      7
    • Publisher
      Springer
    • Related Report
      2014 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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