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Modeling the neuronal phenotype of epileptic encephalopathy using patient-derived iPSCs

Research Project

Project/Area Number 25870617
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pediatrics
Neurochemistry/Neuropharmacology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

CHIYONOBU Tomohiro  京都府立医科大学, 医学(系)研究科(研究院), 助教 (40571659)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsてんかん性脳症 / iPS細胞 / STXBP1 / STXBPI / PIGW
Outline of Final Research Achievements

We generated iPSC lines from a patient with Ohtahara syndrome (OS) harboring a heterozygous nonsense mutation of STXBP1 and performed neuronal differentiation. Both STXBP1 mRNA and STXBP1 protein expression levels of OS-derived neurons were approximately 50% lower than that of control-derived neurons, proving that OS-derived neurons are a suitable model for elucidating the pathophysiology of STXBP1 haploinsufficiency. Through western blot assays, we found that OS-derived neurons show reduced levels of syntaxin-1, a component of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. In addition, OS-derived neurons have impaired neurite outgrowth. In conclusion, this model enables us to investigate the neurobiology of STXBP1 encephalopathy throughout the stages of neurodevelopment. Reduced expression of STXBP1 leads to changes in the expression of syntaxin-1 that may contribute to the devastating phenotype of STXBP1 encephalopathy.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (3 results)

All 2014

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (2 results)

  • [Journal Article] Glycosylphosphatidylinositol (GPI) anchor deficiency caused by mutations in PIGW is associated with West syndrome and hyperphosphatasia with mental retardation syndrome.2014

    • Author(s)
      Chiyonobu T, Inoue N, Morimoto M, Kinoshita T, Murakami Y
    • Journal Title

      Journal of Medical Genetics

      Volume: 51 Pages: 203-207

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Inherited GPI anchor deficiency: biochemical, molecular, and clinical presentation of a patient with PIGW mutation.2014

    • Author(s)
      Chiyonobu T, Inoue N, Morimoto M, Kinoshita T, Murakami Y
    • Organizer
      American Society of Human Genetics 64th Annual Meeting
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2014-10-18 – 2014-10-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] Inherited GPI anchor deficiency is associated with West syndrome.2014

    • Author(s)
      Chiyonobu T, Inoue N, Morimoto M, Kinoshita T, Murakami Y
    • Organizer
      The 16th Annual Meeting of Infantile Seizure Society
    • Place of Presentation
      Cappadocia, Turkey
    • Year and Date
      2014-06-23 – 2014-06-25
    • Related Report
      2014 Annual Research Report

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Published: 2014-07-25   Modified: 2019-07-29  

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