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Analysis of Mutation Affecting Liver Development and Function in Mice and Medaka

Research Project

Project/Area Number 16370059
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionTokyo Medical and Dental University (2005)
The University of Tokyo (2004)

Principal Investigator

NISHINA Hiroshi  Tokyo Medical and Dental University, Medical Research Institute, Professor, 難治疾患研究所, 教授 (60212122)

Co-Investigator(Kenkyū-buntansha) WADA Teiji  Tokyo Medical and Dental University, Medical Research Institute, Assistant Professor, 難治疾患研究所, 助手 (80401389)
堅田 利明  東京大学, 大学院・薬学系研究科, 教授 (10088859)
星野 真一  東京大学, 大学院・薬学系研究科, 講師 (40219168)
荒木 保弘  東京大学, 大学院・薬学系研究科, 助手 (60345254)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥15,400,000 (Direct Cost: ¥15,400,000)
Fiscal Year 2005: ¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 2004: ¥8,000,000 (Direct Cost: ¥8,000,000)
KeywordsMAP kinase / SAPK / JNK / liver formation / knockout mice / Medaka / apoptosis / endoderm / stress
Research Abstract

Stress-activated protein kinase/c-Jun NH_2-terminal kinase (SAPK/JNK) is activated by many types of cellular stresses and extracellular signals. Recent studies, including the analysis with knockout mice, have led to progress towards understanding the physiological roles of SAPK/JNK activation in embryonic development in addition to immune responses. SAPK/JNK activation plays essential roles in organ formation during mouse development by regulating cell survival, apoptosis, and proliferation. Two SAPK/JNK activators, SEK1 and MKK7, are required for fetal liver formation and full activation of SAPK/JNK, which responds to various stimuli in an all-or-none manner. Thus, several genes that are crucial for liver formation and function have been isolated in mice and confirmed by reverse genetics. Although a reverse genetic approach is powerful in characterizing function of known genes, knowledge of genes in liver formation and disease is still limited. Therefore, identifying mutations affecti … More ng these aspects will uncover genes required for these processes. Systematic forward genetic screens for mutations affecting liver formation and function such as hepatic bud formation, liver morphogenesis, bile color in the gall bladder, lipid metabolism, and liver laterality have been carried out in Medaka, Oryzias latipes. To isolate mutants that model human liver diseases, we are analyzing these mutations. Among them, kendama (ken) mutation was isolated as a gene that affects the laterality of the liver. ken mutant was viable and fertile with inverted positions of liver and heart, and with inverted spiral of gut. Interestingly, the spleen was almost lost in ken mutant. This phenotype is very similar to human genetic disease 'asplenia' whose gene mutation is still unknown. Furthermore, white livers consisting of bloated and Oil red O-positive hepatocytes were observed in ken mutants. Thus, ken mutation models human disease asplenia and Non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). Especially, NAFLD and NASH are serious human diseases in the modern world, so ken mutation may shed a new light on the molecular mechanisms of these diseases and the preventive medicine. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (21 results)

All 2005 2004

All Journal Article (17 results) Book (4 results)

  • [Journal Article] Novel role of the small GTPase Rheb : Its implication in endocytic pathway independent of the activation of mammalian target of rapamycin.2005

    • Author(s)
      Kota Saito, et al.
    • Journal Title

      J. Biochem. 137

      Pages: 423-430

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Human homologue of Maid (HHM) is a useful marker protein in hepatocarcinogenesis.2005

    • Author(s)
      Taro Takami, et al.
    • Journal Title

      Gastroenterology 128

      Pages: 1369-1380

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Fibroblast growth factor 2 facilitates the differentiation of transplanted bone marrow cells into hepatocytes.2005

    • Author(s)
      Tsuyoshi Ishikawa, et al.
    • Journal Title

      Cell Tissue Res. 14

      Pages: 1-11

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Autoamplification of NFATc1 determines its essential role in bone homeostasis.2005

    • Author(s)
      Masataka Asagiri, et al.
    • Journal Title

      J. Exp. Med. 202

      Pages: 1261-1269

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Lesson from the GFP/CCl4 model-Translational Research Project : the development of cell therapy using autologous bone marrow cells in patients with liver cirrhosis.2005

    • Author(s)
      Shuji Terai, et al.
    • Journal Title

      J. Hep. Panc. Surg. 12

      Pages: 203-207

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Development of cell therapy using autologous bone marrow cells for liver cirrhosis.2005

    • Author(s)
      Isao Sakaida, et al.
    • Journal Title

      Med Mol Morphol. 38

      Pages: 197-202

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Novel role of the small GTPase Rheb : Its implication in endocytic pathway independent of the activation of mammalian target of rapamycin.2005

    • Author(s)
      Kota Saito, et al.
    • Journal Title

      J.Biochem. 137

      Pages: 423-430

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Autoamplification of NFATc1 determines its essential role in bone homeostasis2005

    • Author(s)
      Masataka Asagiri, et al.
    • Journal Title

      J.Exp.Med. 202

      Pages: 1261-1269

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Lesson from the GFP/CC14 model-Translational Research Project : the development of cell therapy using autologous bone marrow cells in patients with liver cirrhosis.2005

    • Author(s)
      Shuji Terai, et al.
    • Journal Title

      J.Hepat.Panc.Surg. 12

      Pages: 203-207

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Autoamplification of NFATcl determines its essential role in bone homeostasis.2005

    • Author(s)
      Masataka Asagiri, et al.
    • Journal Title

      J.Exp.Med. 202

      Pages: 1261-1269

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Lesson from the GFP/CC14 model-Translational Research Project : the development of cell therapy using autologous bone marrow cells in patients with liver cirrhosis.2005

    • Author(s)
      Shuji Terai, et al.
    • Journal Title

      J.Hep.Panc.Surg. 12

      Pages: 203-207

    • Related Report
      2005 Annual Research Report
  • [Journal Article] MKK7 couples stress signaling to G2/M cell cycle progression and cellular senescence.2004

    • Author(s)
      Teiji Wada, et al.
    • Journal Title

      Nat.Cell Biol. 6

      Pages: 215-226

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Stress induces mitochondria-mediated apoptosis independent of SAPK/JNK activation in ES cells.2004

    • Author(s)
      Gen Nishitai, et al.
    • Journal Title

      J.Biol.Chem 279

      Pages: 1621-1626

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A subpopulation of bone marrow cells depleted by a novel antibody, anti-Liv8, is useful for cell therapy to repair damaged liver.2004

    • Author(s)
      Naoki Yamamoto, et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 313

      Pages: 1110-1118

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mutations affecting liver development and function in Medaka, Oryzias latipes, screened by multiple criteria.2004

    • Author(s)
      Tomomi Watanabe, et al.
    • Journal Title

      Mech.Dev. 121

      Pages: 791-802

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Requirement of MKK4 and MKK7 for CdCl2- or HgCl_2-induced activation of c-Jun NH_2-terminal kinase in mouse embryonic stem cells.2004

    • Author(s)
      Masato Matsuoka, et al.
    • Journal Title

      Toxicol.Lett. 152

      Pages: 175-181

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Transplantation of bone marrow cells reduces CCl_4-induced liver fibrosis in mice.2004

    • Author(s)
      Isao Sakaida, et al.
    • Journal Title

      Hepatology 40

      Pages: 1304-1311

    • Related Report
      2004 Annual Research Report
  • [Book] The JNK Signaling Pathway2005

    • Author(s)
      Hiroshi Nishina, et al.
    • Total Pages
      93
    • Publisher
      Landes Bioscience, Texas, USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] The Biological Function of JNKKs (MKK4/MKK7 Knockout Mice) in The JNK Signaling Pathway (Anning Lin, eds)2005

    • Author(s)
      Hiroshi Nishina, et al.
    • Total Pages
      93
    • Publisher
      Landes Bioscience, Texas
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] The JNK Signaling Pathway2005

    • Author(s)
      Hiroshi Nishima, et al.
    • Total Pages
      93
    • Publisher
      Landes Bioscience, Texas, USA
    • Related Report
      2005 Annual Research Report
  • [Book] Stem Cell and Liver Regeneration2004

    • Author(s)
      Hiroshi Nishina, et al.
    • Total Pages
      100
    • Publisher
      Springer-Verlag Tokyo, Inc.
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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