A study for molecular pathomechanism of neurodevelopment disorders causing epigenetic dysfunction

2015 Fiscal Year Final Research Report

• Project/Area Number: 24390270
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Masayuki Itoh 国立研究開発法人国立精神・神経医療研究センター, 神経研究所疾病研究第二部, 室長 (50243407)
• Co-Investigator(Kenkyū-buntansha): MATSUDA Junichirou 国立研究開発法人 医薬基盤・健康・栄養研究所, 難病・疾患資源研究部, 研究リーダー (60181731) ; TAKAHASHI Satoshi 国立大学法人 旭川医科大学, 医学部小児科学, 講師 (10431404)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: エピゲノム / 発達障害 / レット症候群 / MeCP2 / IGFBP3

Outline of Final Research Achievements

Neurodevelopmental disorders contain many systemic-epigenome disrupted diseases, like Rett syndrome (RTT). As well-known, epigenome-system in brain plays an important role in control of mental state. On the other hand, the abnormality of MECP2 gene, that is major causative gene of RTT and its product mainly works transcription repressor, presents two different phenotypes of RTT and Angelman syndrome. Moreover, it has been reported strongly functional relationship of MECP2 gene and chromosome 15q11-q13 (AS-PWS imprinting region).
In the present study, we performed MeCP2 functional analyses and recovery study, using original mecp2-expression control mice and multiple approaches. As the results, we revealed that molecular pathophysiology of abnormal MeCP2 gene and discovered some candidate factors to be mild phenotypes of RTT and critical period for any treatment. From the study, we could learn the important factors of epigemone system in developmental disorders.

Free Research Field

発達病態学