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Functional analysis of Trib1/2 double knockout mice on hematopoiesis

Research Project

Project/Area Number 23790451
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Experimental pathology
Research InstitutionJapanese Foundation For Cancer Research

Principal Investigator

YOKOYAMA Takashi  公益財団法人がん研究会, がん研究所発がん研究部, 研究員 (00535833)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
KeywordsTrib1 / Trib2 / C/EBPα / ノックアウトマウス / MAPキナーゼ経路 / 白血病 / 造血 / C/EBPa / 顆粒球分化 / IL6r
Research Abstract

Overexpression of Trib1 or Trib2 induces acute myeloid leukemia (AML). We have previously reported that enhancement of MAP kinase pathway through interaction of Trib1 with MEK1 and degradation of C/EBPα is required for leukemic activity of Trib1. However Trib1 or Trib2 KO (knockout) mice did not indicate severely abnormal phenotype and it is no clear the Trib1/2 function in normal tissues. In this study, we demonstrated that Trib1 and Trib2 show different expression pattern in many tissues of E13.5 embryo and adult mice. In addition, bone marrow of Trib1 KO mice indicated increase of segmented neutrophils, C/EBPα protein and its target genes that induce granulopoiesis. These results suggest that Trib1 regulates granulopoiesis through degradation of C/EBPα. On the other hand, Trib2 KO mice did not show abnormal differentiation and Trib1/2 double conditional KO indicated the same level of granulopoiesis as Trib1 single KO. In normal bone marrow cells, expression of Trib1 is about 5 fold by compared with Trib2, indicating Trib1 dominantly plays a key role in regulation of granulopoiesis

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (17 results)

All 2012 2011 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (13 results) Remarks (3 results)

  • [Journal Article] Identification of TRIB1 R107L gain-of-function mutation in human acute megakaryocytic leukemia2012

    • Author(s)
      Yokoyama T, Toki T, Aoki Y, Kanezaki R, Park MJ, Kanno Y, Takahara T, Yamazaki Y, Ito E, Hayashi Y, Nakamura T.
    • Journal Title

      Blood

      Volume: 119 Issue: 11 Pages: 2608-2611

    • DOI

      10.1182/blood-2010-12-324806

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Sytl1はAML発症におけるMeis1の新規標的遺伝子でありHoxa9に協調作用を示す2012

    • Author(s)
      横山隆志,中武真由香,菅野陽平,高原智子,山崎ゆかり,堤修一,油谷浩幸,中村卓郎
    • Organizer
      第71回 日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      2012-09-20
    • Related Report
      2012 Final Research Report
  • [Presentation] Sytl1 is a novel Meis1 target and a cooperative partner of Hoxa9 in AML development2012

    • Author(s)
      Takashi Yokoyama, Mayuka Nakatake, Yohei Kanno, Tomoko Takahara, Yukari Yamazaki, Shuichi Tsutsumi, Hiroyuki Aburatani and Takuro Nakamura
    • Organizer
      9th International Workshop on Molecular Aspects of Myeloid Stem Cell Development and Leukemia
    • Place of Presentation
      アメリカ合衆国オハイオ州シンシナティ
    • Year and Date
      2012-05-07
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] 白血病原因遺伝子Trib1/2の発現と造血における役割2012

    • Author(s)
      横山隆志,山崎ゆかり,菅野陽平,高原智子,西中村 隆一,中村卓郎
    • Organizer
      第101回 日本病理学会総会
    • Place of Presentation
      新宿
    • Year and Date
      2012-04-27
    • Related Report
      2012 Final Research Report
  • [Presentation] TRIB1 gain-of-function mutation in Down syndrome-related leukemia2011

    • Author(s)
      Takashi Yokoyama, Tsutomu Toki, Yoshihiro Aoki, Rika Kanezaki, Myoung-ja Park, Etsuro Ito, Yasuhide Hayashi and Takuro Nakamura
    • Organizer
      第70回 日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-05
    • Related Report
      2012 Final Research Report
  • [Presentation] Trib1による白血病発症機構.平成23年度 文科省科研費補助金2011

    • Author(s)
      横山隆志,菅野陽平,山崎ゆかり,高原智子,宮田敏, 林泰秀,伊藤悦朗, 中村卓郎
    • Organizer
      新学術領域 「がん研究分野の特性等を踏まえた支援活動」 がん若手研究者ワークショップ
    • Place of Presentation
      蓼科
    • Year and Date
      2011-09-03
    • Related Report
      2012 Final Research Report
  • [Presentation] Trib1によるMEK1/ERK経路とC/EBPα制御を介した 白血病発症機構の解明2011

    • Author(s)
      横山隆志,菅野陽平,山崎ゆかり,高原智子,宮田敏, 林泰秀,伊藤悦朗, 中村卓郎
    • Organizer
      第7回 血液学若手研究者勉強会(麒麟塾)
    • Place of Presentation
      東京
    • Year and Date
      2011-06-04
    • Related Report
      2012 Final Research Report
  • [Presentation] ダウン症候群関連急性巨核球性白血病におけるTRIB1変異の同定2011

    • Author(s)
      横山隆志,中村卓郎
    • Organizer
      第100回 日本病理学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2011-04-29
    • Related Report
      2012 Final Research Report 2011 Research-status Report
  • [Presentation] Trib1によるMEK1/ERK経路とC/EBPα制御を介した 白血病発症機構の解明2011

    • Author(s)
      横山 隆志,菅野 陽平,山崎 ゆかり,高原 智子,宮田 敏, 林 泰秀,伊藤 悦朗, 中村 卓郎
    • Organizer
      第7回 血液学若手研究者勉強会(麒麟塾)
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Presentation] Trib1による白血病発症機構2011

    • Author(s)
      横山 隆志,菅野 陽平,山崎 ゆかり,高原 智子,宮田 敏, 林 泰秀,伊藤 悦朗, 中村 卓郎
    • Organizer
      平成23年度 文科省科研費補助金 新学術領域 「がん研究分野の特性等を踏まえた支援活動」 がん若手研究者ワークショップ
    • Place of Presentation
      蓼科
    • Related Report
      2011 Research-status Report
  • [Presentation] TRIB1 gain-of-function mutation in Down syndrome-related leukemia.2011

    • Author(s)
      Takashi Yokoyama, Tsutomu Toki, Yoshihiro Aoki, Rika Kanezaki, Myoung-ja Park, Etsuro Ito, Yasuhide Hayashi and Takuro Nakamura.
    • Organizer
      第70回 日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] 白血病原因遺伝子Trib1/2の発現と造血における役割

    • Author(s)
      横山 隆志,山崎 ゆかり,管野陽平,高原智子,西中村 隆一,中村 卓郎
    • Organizer
      第101回 日本病理学会総会
    • Place of Presentation
      新宿
    • Related Report
      2012 Annual Research Report
  • [Presentation] Sytl1はAML発症におけるMeis1の新規標的遺伝子でありHoxa9に協調作用を示す

    • Author(s)
      横山 隆志,中武 真由香,管野陽平,高原智子,山崎 ゆかり,堤 修一,油谷 浩幸,中村 卓郎
    • Organizer
      第71回 日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Annual Research Report
  • [Presentation] Meis1標的遺伝子Sytl1の白血病発症における役割

    • Author(s)
      横山 隆志、中武 真由香、倉田 盛人、中村 卓郎
    • Organizer
      第17回 造血器腫瘍研究会 兼 がん研究開発費「がん幹細胞に対する新規分子標的治療薬の開発を目指した基盤研究」班会議
    • Place of Presentation
      宮崎
    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.jfcr.or.jp/laboratory/department/carcinogenesis/index.html

    • Related Report
      2012 Final Research Report
  • [Remarks] 発がん研究部 部門紹介

    • URL

      http://www.jfcr.or.jp/laboratory/department/carcinogenesis/

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.jfcr.or.jp/laboratory/department/carcinogenesis/index.html

    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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