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Restricted growth and insulin-like growth factor-1 deficiency in mice lacking presenilin-1 in the neural crest cell lineage

Research Project

Project/Area Number 20591104
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionMatsuyama University

Principal Investigator

NAKAJIMA Mitsunari  Matsuyama University, 薬学部, 准教授 (70311404)

Co-Investigator(Kenkyū-buntansha) FURUKAWA Yoshiko  松山大学, 薬学部, 教授 (20219108)
OKUYAMA Satoshi  松山大学, 薬学部, 助教 (40550380)
加来 鉄平  松山大学, 薬学部, 助教 (20435077)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsプレセニリン1 / アルツハイマー病 / 神経堤 / 下垂体 / 成長ホルモン
Research Abstract

Presenilin-1 (PS1) is a transmembrane protein that is in many cases responsible for the development of early-onset familial Alzheimer's disease. PS1 is essential for neurogenesis, somitogenesis, angiogenesis, and cardiac morphogenesis. We report here that PS1 is also required for maturation and/or maintenance of the pituitary gland. We generated PS1-conditional knockout (PS1-cKO) mice by crossing floxed PS1 and Wnt1-cre mice, in which PS1 was lacking in the neural crest-derived cell lineage. Although the PS1-cKO mice exhibited no obvious phenotypic abnormalities for several days after birth, reduced body weight in the mutant was evident by the age of 3 to 5 weeks. Pituitary weight and serum insulin-like growth factor (IGF)-1 level were also reduced in the mutant. Histologic analysis revealed severe atrophy of the cytosol in the anterior and intermediate pituitary lobes of the mutant. Immunohistochemistry did not reveal clear differences in the expression levels of thyroid-stimulating hormone, adrenocorticotropic hormone, or prolactin in the mutant pituitary. In contrast, growth hormone expression levels were reduced in the anterior lobe of the mutant. PS1 was defective in the posterior lobe, but not the anterior or intermediate lobes, in the mutant pituitary. These findings suggest that PS1 indirectly mediates the development and/or maintenance of the anterior and intermediate lobes in the pituitary gland via actions in other regions, such as the posterior lobe.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (14 results)

All 2011 2010 2009 2008 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (3 results) Remarks (1 results)

  • [Journal Article] Hydrocephalus and abnormal subcommissural organ in mice lacking presenilin-1 in Wnt1 cell lineages.2011

    • Author(s)
      Nakajima M, Matsuda K, Miyauchi N, Fukunaga Y, Watanabe S, Okuyama S, Perez J, Fernandez-Llebrez P, Shen J, Furukawa Y.
    • Journal Title

      Brain Res. 1382巻

      Pages: 275-281

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hydrocephalus and abnormal subcommissural organ in mice lacking presenilin-l in Wntl cell lineages.2011

    • Author(s)
      Mitsunari Nakajima
    • Journal Title

      Brain Res.

      Volume: 1382 Pages: 275-281

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Estrogen Stimulates Proliferation and Differentiation of Neural Stem/Progenitor Cells through Different Signal Transduction Pathways.2010

    • Author(s)
      Okada M, Makino A, Nakajima M, Okuyama S, Furukawa S, Furukawa Y.
    • Journal Title

      Int J Mol Sci. 11巻

      Pages: 4114-4123

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 4-Methylcatechol-induced heme oxygenase-1 exerts a protective effect against oxidative stress in cultured neural stem/progenitor cells via PI3 kinase/Akt pathway.2010

    • Author(s)
      Furukawa Y, Urano T, Minamimura M, Nakajima M, Okuyama S, Furukawa S.
    • Journal Title

      Biomed Res. 31巻

      Pages: 45-52

    • NAID

      130004903782

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Estrogen Stimulates Proliferation and Differentiation of Neural Stem/Progenitor Cells through Different Signal Transduction Pathways.2010

    • Author(s)
      Makiko Okada
    • Journal Title

      Int J Mol Sci.

      Volume: 11 Pages: 4114-4123

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 4-Methylcatechol-induced heme oxygenase-1 exerts a protective effect against oxidative stress in cultured neural stem/progenitor cells via PI3 kinase/Akt pathway2010

    • Author(s)
      Furukawa Y, Urano T, Minamimura M, Nakajima M, Okuyama S, Furukawa S.
    • Journal Title

      Biomedical Research 31

      Pages: 45-52

    • NAID

      130004903782

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Restricted growth and insulin-like growth factor-1 deficiency in mice lacking presenilin-1 in the neural crest cell lineage.2009

    • Author(s)
      Nakajima M, Watanabe S, Okuyama S, Shen J, Furukawa Y
    • Journal Title

      Int J Dev Neurosci. 27巻

      Pages: 837-843

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Restricted growth and insulin-like growth factor-1 deficiency in mice lacking presenilin-1 in the neural crest cell lineage2009

    • Author(s)
      Nakajima M, Watanabe S, Okuyama S, Shen J, Furukawa Y.
    • Journal Title

      International Journal of Developmental Neuroscience 27

      Pages: 837-843

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of estrogens on proliferation and differentiation of neural stem/progenitor cells.2008

    • Author(s)
      Okada M, Murase K, Makino A, Nakajima M, Kaku T, Furukawa S, Furukawa Y
    • Journal Title

      Biomed Res. 29巻

      Pages: 163-170

    • NAID

      130004470710

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of estrogens on proliferation and differentiation of neural stem/progenitor cells.2008

    • Author(s)
      Okada M, Murase K, Makino A, Nakajima M, Kaku T, Furukawa s, Furukawa Y.
    • Journal Title

      Biomedical Research 29

      Pages: 163-170

    • NAID

      130004470710

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 4-メチルカテコールはHO-1発現誘導により神経幹/前駆細胞を酸化ストレスから保護する2010

    • Author(s)
      古川美子、浦野友美、南村美里、中島光業、奥山聡、古川昭栄
    • Organizer
      日本薬学会
    • Place of Presentation
      岡山市
    • Year and Date
      2010-03-30
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] 下垂体成長ホルモン産生細胞の成熟・維持におけるプレセニリン1の働き2009

    • Author(s)
      中島光業、奥山聡、渡辺苑、古川美子
    • Organizer
      日本薬理学会西南部会
    • Place of Presentation
      松山市
    • Year and Date
      2009-11-27
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] 神経堤細胞特異的プレセニリン1欠損による成長ホルモン分泌不全症モデルマウスの作製2008

    • Author(s)
      中島光業、渡辺苑、加来鉄平、古川美子
    • Organizer
      日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://ghp01.matsuyama-u.ac.jp/~yakugaku/laboratory/labo_pharmacology.html

    • Related Report
      2010 Final Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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