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2006 Fiscal Year Final Research Report Summary

Abnormal development of the central nervous system of the knockout mouse that becomes obese

Research Project

Project/Area Number 17590168
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General anatomy (including Histology/Embryology)
Research InstitutionYokohama City University

Principal Investigator

IKEDA Yayoi  Yokohama City University, School of Medicine, Associate Professor, 医学部, 準教授 (00202903)

Co-Investigator(Kenkyū-buntansha) IKEDA Masaaki  Tokyo Medical and Dntal University Graduate School, Associate Professor, 大学院医歯学総合研究科, 助教授 (20193211)
Project Period (FY) 2005 – 2006
Keywordsnuclear receptor / ventromedial hypothalamus / Steroidogenic factor 1 (SF-1) / obesity / central nervous system / conditional knockout
Research Abstract

Steroidogenic factor 1 (SF-1) is an orphan nuclear receptor that plays key roles in adrenal and gonadal development, expression of pituitary gonadotropins, and development of the ventromedial hypothalamic nucleus (VMH). If kept alive by adrenal transplantation, SF-1 knockout (KO) mice develop a metabolic syndrome characterized by delayed-onset obesity and decreased locomotor activity, with no change in food consumption. To define specific roles of SF-1 in the VMH, we used the Cre-loxP system to inactivate SF-1 in a CNS-specific manner. Using the nestin-Cre transgene, which inactivates SF-1 during embryogenesis, we largely recapitulated the VMH structural defect seen in the global SF-1 KO mice. These CNS-specific SF-1 KO mice had decreased locomotor activity and became obese on a high-fat diet. In behavioral tests felt to measure anxiety, they were significantly more "anxious" than wild-type littermates. In addition, CNS-specific SF-1 KO mice had considerably decreased expression in the region of the VMH of several genes, including brain-derived neurotrophic factor (BDNF), the type 2 receptor for corticotropin-releasing hormone (CRF-R_2), and the leptin receptor. These findings reveal important roles of SF-1 in the hypothalamic expression of key regulators of body weight and anxiety, providing a plausible molecular explanation for the phenotype caused by CNS-specific KO of SF-1.

  • Research Products

    (9 results)

All 2006 2005 Other

All Journal Article (9 results)

  • [Journal Article] Differential expression of the estrogen receptors alpha and beta during postnatal development of the rat cerebellum2006

    • Author(s)
      Yayoi Ikeda
    • Journal Title

      Brain Res. 1083

      Pages: 39-49

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 脳の性分化に影響を与えるステロイドホルモンと関連物質2006

    • Author(s)
      池田やよい
    • Journal Title

      平成17年度環境ホルモン研究報告 8号

      Pages: 57-60

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Differential expression of the estrogen receptors alpha and beta during postnatal development of the rat cerebellum2006

    • Author(s)
      Ikeda, Y., Nagai, A.
    • Journal Title

      Brain Res. 1083

      Pages: 39-49

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] 脳の性分化における分子機構-視床下部腹内側核(VMH)における転写因子SF-1の役割2005

    • Author(s)
      池田 やよい
    • Journal Title

      性差と医療 2

      Pages: 153-156

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Ubc9 and protein inhibitor of activated STAT 1 activate Chicken Ovalbumin Upstream Promoter-Transcription Factor I-mediated human CYP11B2 gene transcription2005

    • Author(s)
      Isao Kurihara
    • Journal Title

      The Journal of Biological Chemistry 230・8

      Pages: 6721-6730

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Molecular Mechanism of Sex Differentiation of the Brain : SF-1 in the Ventromedial Hypothalamus2005

    • Author(s)
      Ikeda, Y., Zhao, L., Hayashi, S., Parker, K.L.
    • Journal Title

      Gender & Sex Specific Medicine 2

      Pages: 153-156

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Ubc9 and protein inhibitor of activated STAT 1 activate Chicken Ovalbumin Upstream Promoter-Transcription Factor I-mediated human CYP11B2 gene transcription2005

    • Author(s)
      Kurihara, I., Shibata, H., Kobayashi, S., Suda, N., Ikeda, Y., Yokota, K., Murai, A., Saito, I., Rainey, W.E., Saruta, T.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 6721-6730

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cerebellum, a target for hormonal signaling

    • Author(s)
      Noriyuki Koibuchi
    • Journal Title

      The Cerebellum (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cerebellum, a target for hormonal signaling

    • Author(s)
      Koibuchi N., Kimura-Kuroda J., Ikeda Y., Tsutsui K.
    • Journal Title

      The Cerebellum (in press)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2008-05-27  

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