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

2014 Fiscal Year Final Research Report

• Project/Area Number: 25870617
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics; Neurochemistry/Neuropharmacology
• Research Institution: Kyoto 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
• Keywords: てんかん性脳症 / iPS細胞 / STXBP1

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.

Free Research Field

小児神経学