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Analysis of the mechanism causing female infertility in mice deficient midkine and pleiotrophin.

Research Project

Project/Area Number 17590245
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionNagoya University

Principal Investigator

MURAMATSU Hisako  Nagoya University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (50182134)

Co-Investigator(Kenkyū-buntansha) KADOMATSU Kenji  Nagoya University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (80204519)
SATO Masahiro  Kagoshima University, Center For Frontier Science, Professor, フロンティアサイエンス研究推進センター, 教授 (30287099)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsmidkine / pleiotrophin / gene-deficient mouse / female fertility
Research Abstract

Midkine and pleiotrophin form a family of growth factors, and display diverse physiological activities, such as promotion of growth, survival and migration of various cells. Mice deficient in one of the genes show few abnormalities upon reproduction and development. To understand their roles in these processes, we produced mice deficient in both genes; the double deficient (DKO) mice were born in only 1/3 the number expected by Mendelian segregation, and 4 weeks after birth weighed about half as much as wild-type (WT) mice. Most of the female double deficient mice were infertile.
In these mice, the numbers of mature follicles and of ova at ovulation were reduced compared to numbers in WT mice. Both midkine and pleiotrophin were expressed in the follicular epithelium and granulosa cells of the ovary. The expression of these factors in the uterus was dramatically altered during the estrous cycle. The diestrus and proestrus periods were long and the estrus period was short in the DKO mice, indicating the role of the factors in the estrous cycle. Furthermore, vaginal abnormality was found in about half of DKO mice. All DKO mice with an abnormal vagina were sterile, without any sign of a plug. Furthermore, we found that DKO mice had a thin vaginal epithelium as compared to age-matched WT mice. These abnormalities in combination resulted in female infertility. Therefore, midkine and pleiotrophin as well as their signaling receptors play important roles in the female reproductive system.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (19 results)

All 2006 2005

All Journal Article (19 results)

  • [Journal Article] Midkine, a heparin-binding growth factor, produced by the host enhances metastasis of Lewis lung carcinoma cells.2006

    • Author(s)
      Salama, R.H.M. ら
    • Journal Title

      Cancer Lett. 233

      Pages: 16-20

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Doxorubicin-conjugated anti-midkine monoclonal antibody as a potential anti-tumor drug.2006

    • Author(s)
      Inoh, K. ら
    • Journal Title

      Jpn. J. Clin. Oncol. 36

      Pages: 207-211

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Mice doubly deficient in the midkine and pleiotrophin genes exhibit deficits in the expression of _-tectorin gene and in auditory response.2006

    • Author(s)
      Zou, P. ら
    • Journal Title

      Lab. Invest. 86

      Pages: 645-653

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Midkine, a heparin-binding growth factor, is expressed in neural precursor cells and promotes their growth.2006

    • Author(s)
      Zou, P. ら
    • Journal Title

      J. Neurochem. 99

      Pages: 1470-1479

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Female infertility in mice deficient in midkine and pleiotrophin, which form a distinct family of growth factors.2006

    • Author(s)
      Muramatsu, H. ら
    • Journal Title

      Genes Cells 11

      Pages: 1405-1417

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Midkine as a molecular Target : Comparison of effects of chondroitin sulfate E and siRNA.2006

    • Author(s)
      Yamamoto, H. ら
    • Journal Title

      Biochem. Biophys. Res. Commun. 351

      Pages: 915-919

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Midkine, a heparin-binding growth factor, produced by the host enhances metastasis of Lewis lung carcinoma cells.2006

    • Author(s)
      Salama, R.H.M.et al.
    • Journal Title

      Cancer Lett. 233

      Pages: 16-20

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Doxorubicin-conjugated anti-midkine monoclonal antibody as a potential anti-tumor drug.2006

    • Author(s)
      Inoh, K. et al.
    • Journal Title

      Jpn.J.Clin.Oncol. 36

      Pages: 207-211

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mice doubly deficient in the midkine and pleiotrophin genes exhibit deficits in the expression of β-tectorin gene and in auditory response.2006

    • Author(s)
      Zou, P.et al.
    • Journal Title

      Lab.Invest. 86

      Pages: 645-653

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Midkine, a heparin-binding growth factor, is expressed in neural precursor cells and promotes their growth.2006

    • Author(s)
      Zou, P.et al.
    • Journal Title

      J.Neurochem. 99

      Pages: 1470-1479

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Female infertility in mice deficient in midkine and pleiotrophin, which form a distinct family of growth factors.2006

    • Author(s)
      Muramatsu, H. et al.
    • Journal Title

      Genes Cells. 11

      Pages: 1405-1417

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Midkine as a molecular Target : Comparison of effects of chondroitin sulfate E and siRNA.2006

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

      Biochem.Biophys.Res.Commun. 351

      Pages: 915-919

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Midkine, a heparin-binding growth factor, produced by the host enhances metastasis of Lewis lung carcinoma cells.2006

    • Author(s)
      Salama, R. H. M ら
    • Journal Title

      Cancer Lett. 233

      Pages: 16-20

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Mice doubly deficient in the midkine and pleiotrophin genes exhibit deficits in the expression of β-tectorin gene and in auditory response.2006

    • Author(s)
      Zou, P. ら
    • Journal Title

      Lab. Invest. 86

      Pages: 645-653

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Female infertility in mice deficient in midkine and pleiotrophin, which form a distinct family of growth factors..2006

    • Author(s)
      Muramatsu, H. ら
    • Journal Title

      Genes Cells 11

      Pages: 1405-1417

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Abnormalities caused by carbohydrate alterations in I-_-6-N-acetylglucosaminyltransferase-deficient mice.2005

    • Author(s)
      Chen, G-Y ら
    • Journal Title

      Mol. Cell. Biol. 25

      Pages: 7828-7838

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Abnormalities caused by carbohydrate alterations in I-β-6-N-acetylglucosaminyltransferase-deficient mice2005

    • Author(s)
      Chen, G-Y. et al.
    • Journal Title

      Mol Cell.Biol. 25

      Pages: 7828-7838

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Abnormalities caused by carbohydrate alterations in Iβ6-N-acetylglucosaminyltransferase-deficient mice.2005

    • Author(s)
      Chen, G-Y.ら
    • Journal Title

      Mol.Cell.Biol. 25

      Pages: 7828-7838

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Increased midkine levels in sera from patients with Alzheimer's disease.2005

    • Author(s)
      Sarama, R.H.M. ら
    • Journal Title

      Prog.Neuro-psychoph. 29

      Pages: 611-616

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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