Molecular mechanism of autism based on abnormalities of synaptic genes expression using iPS cells of Rett syndrome

• Project/Area Number: 25860852
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: University of Yamanashi
• Principal Investigator: MIYAKE Kunio 山梨大学, 総合研究部, 助教 (60550712)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: エピジェネティクス / 発達障害 / レット症候群 / iPS細胞 / DNAメチル化 / ヒストン修飾 / 自閉症 / ＭＥＣＰ２ / MeCP2

Outline of Final Research Achievements

We investigated the expression mechanisms of MeCP2 target genes in the neuronal cell lines and induced pluripotent stem cells (iPSCs) derived from Rett syndrome patients. As a result, we found that Lin7a gene was activated by MeCP2. Furthermore, we found that gene expression pattern was different between MeCP2 positive iPSCs-derived neural cells and MeCP2 negative cells. These results suggest that MeCP2 has an important function during neuronal differentiation and synaptic maturation.

Research Products

• [Journal Article] Understanding the epigenetics of neurodevelopmental disorders and DOHaD (2015)
  • Author(s): Kubota T, Miyake K, Hariya N, Mochizuki K
  • Journal Title: J Dev Orig Health Dis Volume: 1 Pages: 1-9
• [Journal Article] A Female Patient with Incomplete Hemophagocytic Lymphohistiocytosis Caused by a Heterozygous XIAP Mutation Associated with Non-Random X-Chromosome Inactivation Skewed Towards the Wild-Type XIAP Allele (2015)
  • Author(s): Yang X, Hoshino A, Taga T, Kunitsu T, Ikeda Y, Yasumi T, Yoshida K, Wada T, Miyake K, Kubota T, Okuno Y, Muramatsu H, Adachi Y, Miyano S, Ogawa S, Kojima S, Kanegane H
  • Journal Title: J Clin Immunol Volume: 35(3) Issue: 3 Pages: 244-8
  • DOI: 10.1007/s10875-015-0144-6
  • Peer Reviewed
• [Journal Article] Molecular mechanism in Rett syndrome (2015)
  • Author(s): Miyake K, Kubota T
  • Journal Title: Folia Pharmacologica Japonica Volume: 145 Issue: 4 Pages: 178-182
  • DOI: 10.1254/fpj.145.178
  • NAID: 130005061558
  • ISSN: 0015-5691, 1347-8397
• [Journal Article] Expressions of tight junction proteins Occludin and Claudin-1 are under the circadian control in the mouse large intestine: implications in intestinal permeability and susceptibility to colitis (2014)
  • Author(s): Kyoko OO, Kono H, Ishimaru K, Miyake K, Kubota T, Ogawa H, Okumura K, Shibata S, Nakao A
  • Journal Title: PLoS One Volume: 9(5) Issue: 5 Pages: e98016-e98016
  • DOI: 10.1371/journal.pone.0098016
  • Peer Reviewed / Open Access
• [Journal Article] 神経疾患のエピゲノム―脳機能障害を理解する新しい指標 (2014)
  • Author(s): 久保田 健夫, 平澤 孝枝, 三宅 邦夫
  • Journal Title: BRAIN and NERVE Volume: 66(5) Pages: 591-7
  • NAID: 40020089078
• [Journal Article] Epigenetics as a basis for diagnosis of neurodevelopmental disorders: challenges and opportunities. (2014)
  • Author(s): Kubota T, Miyake K, Hariya M, Mochizuki K.
  • Journal Title: Expert Rev Mol Diagn Volume: 14 Issue: 6 Pages: 685-697
  • DOI: 10.1586/14737159.2014.925805
  • Peer Reviewed
• [Journal Article] Comparison of genomic and epigenomic expression in monozygotic twins discordant for Rett syndrome (2013)
  • Author(s): Miyake K, Yang C, Minakuchi Y, Ohori K, Soutome M, Hirasawa T, Kazuki Y, Adachi N, Suzuki S, Itoh M, Goto Y, Andoh T, Kurosawa H, Akamatsu W, Oyama M, Okano H, Oshimura M, Sasaki M, Toyoda A, Kubota T
  • Journal Title: PLoS ONE Volume: 8 Issue: 6 Pages: e66729-e66729
  • DOI: 10.1371/journal.pone.0066729
  • Peer Reviewed
• [Journal Article] Oligodendrocyte transcription factor 1 (Olig1) is a Smad cofactor involved in cell motility induced by transforming growth factor-β (2013)
  • Author(s): Motizuki M, Isogaya K, Miyake K, Ikushima H, Kubota T, Miyazono K, Saitoh M, Miyazawa K.
  • Journal Title: Journal of Biological Chemistry Volume: 288 Issue: 26 Pages: 18911-18922
  • DOI: 10.1074/jbc.m113.480996
  • Peer Reviewed / Open Access
• [Journal Article] The role of epigenetics in Rett sydro me (2013)
  • Author(s): Kubota T, Miyake K, Hirasawa T
  • Journal Title: Epigenomics Volume: 5 Issue: 5 Pages: 583-592
  • DOI: 10.2217/epi.13.54
  • Peer Reviewed
• [Presentation] DNA のメチル化修飾を検出できるアニオン交換 HPLC カラムの臨床応用 (2014)
  • Author(s): 22.武居 美沙、三宅 邦夫、山田 有理子、與谷 卓也、久保田 健夫
  • Organizer: 日本人類遺伝学会第５９回大会
  • Place of Presentation: タワーホール船堀 （江戸川区・東京）
  • Year and Date: 2014-11-19 – 2014-11-22
• [Presentation] 発達障害とエピジェネティクス (2014)
  • Author(s): 三宅 邦夫
  • Organizer: 日本ストレス学会学術総会 第30回記念大会
  • Place of Presentation: 日本大学文理学部百周年記念館（世田谷区・東京）
  • Year and Date: 2014-11-07 – 2014-11-08
  • Invited
• [Presentation] Clinical application of an anion exchange HPLC column that distinguishes DNA methylation status (2014)
  • Author(s): K. Miyake, Y. Yamada, T. Yotani, T. Kubota
  • Organizer: ASHG
  • Place of Presentation: San Diego （USA)
  • Year and Date: 2014-10-18 – 2014-10-22
• [Presentation] Change of neuronal gene expression by administration of various anti-depressant in primary neocortical neurons (2014)
  • Author(s): N. A. Nguyen, K. Miyake, T. Kubota
  • Organizer: ASHG
  • Place of Presentation: San Diego （USA)
  • Year and Date: 2014-10-18 – 2014-10-22
• [Presentation] 変異体マウスを用いた翻訳伸長因子遺伝子欠損の血液学的影響 (2014)
  • Author(s): 18.庄司 陽平,久保田 悠一,井上 克枝,久保田 健夫,三宅 邦夫,葛西 宏威,武川 克志,手塚 英夫.
  • Organizer: 第60回日本実験動物学会総会
  • Place of Presentation: つくば国際会議場 (茨城県・つくば市）
  • Year and Date: 2014-05-15 – 2014-05-17
• [Presentation] Rett症候群における病態分子機構 (2014)
  • Author(s): 三宅 邦夫
  • Organizer: 日本薬理学会
  • Place of Presentation: 仙台国際センター （宮城県仙台市）
• [Presentation] Epigenomic differences in monozygotic twins with Rett syndrome (2013)
  • Author(s): 三宅 邦夫
  • Organizer: 日本エピジェネティクス研究会
  • Place of Presentation: 奈良県新公会堂 (奈良県奈良市）
• [Presentation] 重症度差異のある一卵性双生児レット症候群患者におけるエピゲノム比較 (2013)
  • Author(s): 三宅 邦夫
  • Organizer: 日本神経科学会
  • Place of Presentation: 国立京都国際会館 （京都府京都市）
• [Remarks] 環境遺伝医学講座
  • URL: http://www.epigenetmed.com/
• [Remarks] 環境遺伝医学講座
  • URL: http://www.epigenetmed.com/
• [Patent(Industrial Property Rights)] インプリンティング疾患の診断に有効な染色体機能異常の検査方法 (2014)
  • Inventor(s): 久保田健夫、三宅邦夫
  • Industrial Property Rights Holder: 久保田健夫、三宅邦夫
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-165148
  • Filing Date: 2014-08-14
• [Patent(Industrial Property Rights)] 幹細胞の品質管理方法 (2014)
  • Inventor(s): 與谷卓也、山田有里子、砂村栄一郎、久保田健夫、三宅邦夫
  • Industrial Property Rights Holder: 與谷卓也、山田有里子、砂村栄一郎、久保田健夫、三宅邦夫
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-213137
  • Filing Date: 2014-10-17