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2006 Fiscal Year Final Research Report Summary

Clarification of the genetic mechanisms underlying the regulation for the expression of SHOX, a causative gene for short stature and sdyschomndrosteosis

Research Project

Project/Area Number 17591132
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionNational Research Institute for Child Health and Development

Principal Investigator

OGATA Tsutomu  National Research Institute for Child Health and Development, Director, 部長 (40169173)

Co-Investigator(Kenkyū-buntansha) FUKAMI Maki  National Research Institute for Child Health and Development, Chief, 室長 (40265872)
KAGAMI Masayo  National Research Institute for Child Health and Development, Research Fellow, 研究員 (70399484)
WADA Yuka  National Research Institute for Child Health and Development, Research Fellow, 研究員 (80399485)
Project Period (FY) 2005 – 2006
KeywordsSHOX / Regulatory seqiuence / Sex chromosomes / Haploinsufficiency / In silico analysis / Full length cDNA / Enhancer / 3' region
Research Abstract

The main results obtained in the research period is three-folds.
<Identification of the enhancer region for the SHOX expression>
We have previously studied more than 40 patient with Leri-Weill syndrome, and identified SHOX deletion or mutation in 33 patients. In this research period, we found microdeletions at the 3' region of the SHOX gene in flour patients with no demonstrable SHOX mutation. The smallest overlapping deleted region was determined as 39 kb, and in silica analysis disclosed 6 evolutionally conserved sequences within the 39 kb critical region. Thus, we performed luciferase assay with the evolutionally conserved sequences, and identified that a roughly 800 bp sequence has the transactivation function for the SHOX expression. The results suggest for the first time that the enhancer sequence for SHOX is present in the 800 by region, and support the presence of an enhancer disorder Furthermore, the identification of the molecule regulating the enhancer will permit to clarify the molecular network underlying the SHOX deficiency disorders.
<Production of SHOX cDNA>
We produced the full length SHOX cDNA by synthesizing all the sequence. This was because SHOX was not expressed in skeletal tissues available.
<Production of SHOX transgenic mouse>
To evaluate the effects of SHOX on growth, we made SHOX transgenic mouse. Since SHOX is absent in the mouse, this model mouse can be utilized to analyze the effect of gonadal estrogens and GnRH-analog therapy in SHOX overdosage status. Thus, this is the first step for the gene therapy for growth failure.

  • Research Products

    (12 results)

All 2006 2005

All Journal Article (12 results)

  • [Journal Article] Transactivation function of a ~800 bp evolutionally conserved sequence at the SHOX 3' region : implication for the downstream enhancer.2006

    • Author(s)
      Fukami M, Kato F, Tajima T, Yokoya S, Ogata T
    • Journal Title

      American Journal of Human Genetics 78 (1)

      Pages: 167-170

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Clinical lessons from SHOX mutation research2006

    • Author(s)
      Ogata T, Fukami M
    • Journal Title

      International Growth Monitor 16 (1)

      Pages: 2-6

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Genetics of human growth2006

    • Author(s)
      Ogata T.
    • Journal Title

      Clinical Pediatric Endocrinology 15 (2)

      Pages: 45-53

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Genetics of human growth.2006

    • Author(s)
      Ogata T.
    • Journal Title

      Clinical Pediatric Endocrinology 15 (2)

      Pages: 45-53

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Clinical lessons from SHOX mutation research.2006

    • Author(s)
      Ogata T, Fukami M.
    • Journal Title

      International Growth Monitor 16 (1)

      Pages: 2-6

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Transactivation function of a~800 bp evolutionally conserved sequence at the SHOX 3' region : implication for the downstream enhancer.2006

    • Author(s)
      Fukami M, Kato F, Tajima T, Yokoya S, Ogata T.
    • Journal Title

      American Journal of Human Genetics 78 (1)

      Pages: 167-170

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Microdeletion in the SHOX 3' region associated with skeletal phenotypes of Langer mesomelic dysplasia in a 45,X/46,X,r(X) infant and Leri-Weill dyschondrosteosis in her 46,XX mother : implication for the SHOX enhancer2005

    • Author(s)
      Fukami M, Okuyama T, Yamamori S, Nishimura G, Ogata T
    • Journal Title

      American Journal of Medical Genetics A 137 (1)

      Pages: 72-76

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Clinical features in SHOX haploinsufficiency : diagnostic and thera peutic implications2005

    • Author(s)
      Ogata T, Fukami M
    • Journal Title

      Growth, Genetics & Hormones 20 (2)

      Pages: 17-23

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] PTPN11 mutations and genotype-phenotype correlations in Noonanand LEOPARD syndromes2005

    • Author(s)
      Ogata T, Yoshida R
    • Journal Title

      Pediatric Endocrinology Reviews 2 (4)

      Pages: 669-674

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Microdeletion in the SHOX 3' region associated with skeletal phenotypes of Langer mesomelic dysplasia in a 45, X/46, X, r(X) infant and Leri-Weill dyschondrosteosis in her 46, XX mother : implication for the SHOX enhancer.2005

    • Author(s)
      Fukami M, Okuyama T, Yamamori S, Nishimura G, Ogata T.
    • Journal Title

      American Journal of Medical Genetics A 137 (1)

      Pages: 72-76

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Clinical features in SHOX haploinsufficiency : diagnostic and therapeutic implications.2005

    • Author(s)
      Ogata T, Fukami M.
    • Journal Title

      Growth, Genetics & Hormones 20 (2)

      Pages: 17-23

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] PTPN11 mutations and genotype-phenotype correlations in Noonan and LEOPARD syndromes.2005

    • Author(s)
      Ogata T, Yoshida R.
    • Journal Title

      Pediatric Endocrinology Reviews 2 (4)

      Pages: 669-674

    • 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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