• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2007 Fiscal Year Final Research Report Summary

Analysis of Mutation Affecting Liver Function and Regeneration in Model Organisms

Research Project

Project/Area Number 18390021
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionTokyo Medical and Dental University

Principal Investigator

NISHINA Hiroshi  Tokyo Medical and Dental University, Medical Research Institute, Professor (60212122)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Takashi  Tokyo Medical and Dental University, Medical Research Institute, Assistant Professor (80431948)
ASAOKA Yoichi  Tokyo Medical and Dental University, Medical Research Institute, Assistant Professor (10436644)
Project Period (FY) 2006 – 2007
Keywordsliver / development / regeneration / model organism / medaka / knockout mice / MAP kinase / SAPK / JNK
Research Abstract

The liver is an organ with vital functions, including processing and storage of nutrients, maintenance of serum composition, detoxification and bile production. Recently, 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 affecting 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.

  • Research Products

    (10 results)

All 2008 2007 Other

All Journal Article (8 results) (of which Peer Reviewed: 3 results) Presentation (1 results) Remarks (1 results)

  • [Journal Article] Antagonistic control of cell fates by JNK and p38-MAPK signaling.2008

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

      Cell Death Differ. 15

      Pages: 89-93

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Antagonistic control of cell fates by JNK and p38-MAPK signaling2008

    • Author(s)
      Wada T, Stepniak E, Hui L, Leibbrandt A, Katada T, Nishina H, Wagner EF, Penninger JM.
    • Journal Title

      Cell Death Differ 15

      Pages: 89-93

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Liver development and regeneration: from laboratory study to clinical therapy.2007

    • Author(s)
      Shoji Hata, et. al.
    • Journal Title

      Develop. Growth Differ. 49

      Pages: 163-170

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Activation of the JNK patyway by MSTl is essential and sufficient for the induction of chromatin condensation during apoptosis.2007

    • Author(s)
      Seiji Ura, et. al.
    • Journal Title

      Mol. Cell. Biol. 27

      Pages: 5514-5522

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Liver development and regeneration : from laboratory study to clinical therapy. Corresponding author2007

    • Author(s)
      Shoji Hata, Misako Namae and Hiroshi Nishina
    • Journal Title

      Develop. Growth Differ 49

      Pages: 163-170

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Activation of the JNK patyway by MSTI is essential and sufficient for the induction of chromatin condensation during apoptosis2007

    • Author(s)
      Seiji Ura, Hiroshi Nishina. Yukiko Gotoh, and Toshiaki Katada
    • Journal Title

      Mol. Cell. Biol 27

      Pages: 5514-5522

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Osteoclastic estrogen receptor alpha mediates the osteoprotective estrogen action through Fas ligand signaling2007

    • Author(s)
      Nakamura, T., Imai, Y., Matsumoto, T., Sato, S., Takeuchi, K., Igarashi, K., Harada, Y., Azuma, Y., Krust. A., Yamamoto, Y., Nishina, H., Takeda, S., Takayanagi, H., Metzger, D., Kanno. J., Takaoka, K., Martin, TJ., Chambon, P., Kato, S.
    • Journal Title

      Cell 130

      Pages: 811-923

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] (2007) Administration of. Administration of fibroblast growth factor 2 in combination with bone marrow transplantation synergistically improves carbon tetrachloride-induced liver fibrosis in mice2007

    • Author(s)
      Tsuyoshi Ishikawa, Shuji Terai, Yohei Urata, Yoshio Marumoto, Koji Aoyama, Tomoaki Murata, Yuko Mizunaga, Naoki Yamamoto. Hiroshi Nishina, Koh Shinoda, and Isao Sakaida
    • Journal Title

      Cell Tissue Res 327

      Pages: 463-470

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 肝形成および肝機能不全メダカの単離と解析2007

    • Author(s)
      仁科 博史
    • Organizer
      日本再生医療学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-03-13
    • Description
      「研究成果報告書概要(和文)」より
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.tmd.ac.jp/mri/dbio/index.html

URL: 

Published: 2010-02-04  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi