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

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
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥17,120,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2007: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2006: ¥7,500,000 (Direct Cost: ¥7,500,000)
Keywordsliver / development / regeneration / model organism / medaka / knockout mice / MAP kinase / SAPK / JNK / ストレス応答 / 変異メダカ / 肝形成 / 肝再生 / 肝芽細胞 / 内胚葉
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.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (18 results)

All 2008 2007 2006 Other

All Journal Article (15 results) (of which Peer Reviewed: 4 results) Presentation (1 results) Remarks (2 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
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • 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
    • Related Report
      2007 Final Research Report Summary
  • [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
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • 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
    • Related Report
      2007 Final Research Report Summary
    • 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
    • Related Report
      2007 Final Research Report Summary
  • [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
    • Related Report
      2007 Final Research Report Summary
  • [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
    • Related Report
      2007 Final Research Report Summary
  • [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
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Activation of the JNK patyway by MST1 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

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Release of RASSFIC from the nucleus by Daxx degradation links DNA damage and SAPK/JNK activation.2006

    • Author(s)
      Daiju Kitagawa, et al.
    • Journal Title

      EMBO J. 25

      Pages: 3286-3297

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Fibroblast growth factor 2 facilitates the differentiation of transplanted bone marrow cells into hepatocytes.2006

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

      Cell Tissue Res. 323

      Pages: 221-231

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Protemic analysis of serummaker proteins in recipient mice with liver cirrhosis after bone marrow cell transplantation.2006

    • Author(s)
      Yuichiro Yokoyama, et al.
    • Journal Title

      Proteomics 6

      Pages: 2564-2570

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Premature ovarian failure in androgen receptor-deficient mice.2006

    • Author(s)
      Hiroko Shiina, et al.
    • Journal Title

      Proc Natl Acad Sci USA. 103

      Pages: 224-229

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Nuclear Receptor Mediated Gene Regulation through Chromatin Remodelingand Histone Modifications.2006

    • Author(s)
      Masahiko Kishimoto, et al.
    • Journal Title

      Endocrine J. 53

      Pages: 157-172

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 新規核内複合体Daxx-RASSFICはDNA損傷センサーとして機能してシグナルを核から細胞質へと伝達する2006

    • Author(s)
      北川 大樹, ら
    • Journal Title

      細胞工学 25

      Pages: 1178-1179

    • Related Report
      2006 Annual Research Report
  • [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
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

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

    • Related Report
      2007 Final Research Report Summary
  • [Remarks]

    • URL

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

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi