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Generation of iPS cells derived form an Rett syndrome model mouse and drug screening for Rett syndrome using MeCP2 deficient iPS cells

Research Project

Project/Area Number 22591144
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionKurume University

Principal Investigator

TAKAHASHI Tomoyuki  久留米大学, 医学部, 准教授 (20332687)

Co-Investigator(Renkei-kenkyūsha) MATSUISHI Toyojiro  久留米大学, 医学部, 教授 (60157237)
TANAKA Eiichiro  久留米大学, 医学部, 教授 (80188284)
MURAI Yoshinaka  久留米大学, 医学部, 准教授 (40322820)
NISHI Yoshihiro  久留米大学, 医学部, 講師 (20352122)
OKABE Yasunori  久留米大学, 医学部, 助教 (00446098)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsRett 症候群 / Rett症候群 / レット症候群(RTT) / MeCP2 / iPS細胞 / 疾患モデル / 再生医学
Research Abstract

Rett syndrome (RTT) is a neurodevelopmetal disorder associated with mutations in the methyl-CpG?binding protein 2 (MeCP2) gene. MeCP2-deficient mice recapitulate the neurological degeneration observed in RTT patients. The generation of diseased induced pluripotetn stem (iPS) cell is a critical step in understanding the pathogenesis of genetics and complex diseases. Here, we generated RTT-model mouse iPS cell lines from MeCP2-deficient mouse by co-expressing four factors (Oct3/4, Sox2, Klf4, and c-Myc) throughlentiviraldeliveryandsubsequentlydifferentiatedthemintoneuronalcellsfor further analyses. RTT-model iPS cells were characterized for the expression of pluripotent markers and for their ability to differentiate into all three germ layers by forming embryoid bodies in vitro. In addition, SDIA-induced colonies from both WT and RTT-model iPS cell lines generated cells possessing neuronal-like morphologies that expressed neuronal markers microtubule-associated protein 2 (MAP2) an neuron-specific tubulin beta type III. Our RTT-model iPS cell lines provide a powerful tool for both basic neuroscience research and therapeutic applications.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (26 results)

All 2013 2012 2011 2010

All Journal Article (16 results) (of which Peer Reviewed: 15 results) Presentation (8 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Two neonatal cholestsis patients with mutations in the SRD5B1 (AKR1D1) gene: diagnosis and bile acid profiles during chenodeoxycholic acid treatment.2013

    • Author(s)
      Seki, Y., Mizuochi, T., Kimura, A., Takahashi T., Ohtake, A., Hayashi, S., Morimura, T., Ohno, Y., Hoshina, T., Ihara, K., Takei, H., Nittono H., Kurosawa T., Homma K., Hasegawa T., Matsuishi T.
    • Journal Title

      J Inherit Metab Dis

      Volume: 36(3) Issue: 3 Pages: 565-573

    • DOI

      10.1007/s10545-012-9526-6

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of urinary bile acids in a pediatric BRIC-1 patient: Effect of rifampicin treatment2012

    • Author(s)
      Mizuochi T., Kimura A., Tanaka A., Muto A., Nittono H., Seki Y., Takahashi T., Kurosawa T., Kage M., Takikawa H., Matsuishi T.
    • Journal Title

      Clin Chim Acta

      Volume: 413 Issue: 15-16 Pages: 1301

    • DOI

      10.1016/j.cca.2012.04.011

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Alterations of Gene Expression and Glutamate Clearance in Astrocytes Derived from an MeCP2-null Mouse Model of Rett Syndrome2012

    • Author(s)
      Okabe Y, Takahashi T, Mitsumasu C, Kosai K, MD, Tanaka E, Matsuishi T
    • Journal Title

      PLoS ONE

      Volume: 7(4) Issue: 4 Pages: e35354-e35354

    • DOI

      10.1371/journal.pone.0035354

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Alterations of Gene Expression and Glutamate Clearance in Astrocytes Derived from an MeCP2-null Mouse Model of Rett Syndrome2012

    • Author(s)
      Okabe Y., Takahashi T., et al
    • Journal Title

      PLoS One

      Volume: (in press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased plasma type B natriuretic peptide in the acute phase of Kawasaki disease2011

    • Author(s)
      Kishimoto S, Suda K, Teramachi Y, Nishino H, Kudo Y, Ishii H, Iemura M, Takahashi T, Okamura H, Matsuishi T.
    • Journal Title

      Pediatr Int

      Volume: 53 Issue: 5 Pages: 736-41

    • DOI

      10.1111/j.1442-200x.2011.03351.x

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The state of clinical basic research, and future perspectives.2011

    • Author(s)
      Matsuishi T., Yamashita Y., Takahashi T., Nagamitsu S.Rett syndrome
    • Journal Title

      Brain Dev

      Volume: 33(8) Issue: 8 Pages: 627-631

    • DOI

      10.1016/j.braindev.2010.12.007

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rett症候群の病態に関する神経生化学的研究"特集2:自閉症スペクトラム障害の脳機能病態、査読無2011

    • Author(s)
      山下裕史朗・原宗嗣・高橋知之・松石豊次郎
    • Journal Title

      日本生物学的精神医学会誌

      Volume: Vol.22No.1 Pages: 45-49

    • Related Report
      2012 Final Research Report
  • [Journal Article] Rett syndrome : The state of clinical basic research, and future perspectives2011

    • Author(s)
      Matsuishi T., Takahashi T., et al
    • Journal Title

      Brain Dev

      Volume: 33(8) Pages: 627-631

    • NAID

      10031121966

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased Plasma Type B Natriuretic Peptide in The Acute Phase of Kawasaki Disease2011

    • Author(s)
      Kishimoto S., Takahashi T., et al
    • Journal Title

      Pediatr Int

      Volume: 53(5) Pages: 736-741

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rett syndrome : The state of clinical basic research, and future perspectives.2011

    • Author(s)
      Matsuishi T., Takahashi T., et al.
    • Journal Title

      Brain Dev

      Volume: (in press)

    • NAID

      10031121966

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased Plasma Type B Natriuretic Peptide in The Acute Phase of Kawasaki Disease.2011

    • Author(s)
      Kishimoto S., Takahashi T., et al.
    • Journal Title

      Pediatr Int

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] These authors were equally contributed to this work.)Neural Development ofMethyl-CpG-Binding Protein 2 Null Embryonic Stem Cells: A System for Studying Rett Syndrome.2010

    • Author(s)
      *Okabe Y., *Kusaga A., * Takahashi T., Mitsumasu C., Murai Y., Tanaka E., Higashi H., Matsuishi T., Kosai K.
    • Journal Title

      Brain Res

      Volume: 1360 Pages: 17-27

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular genetics and bile acid profiles of 3beta-hydroxy-delta5-C27-steroid dehydrogenase/isomerase deficiency in 2 Japanise patients.2010

    • Author(s)
      Mizuochi T., Kimura A., Ueki I., Takahashi T., Hashimoto T., Takao A., Seki Y., Takei H., Nittono H., Kurosawa T., Matsuishi T.
    • Journal Title

      Pediatr Res

      Volume: 68(3) Pages: 258-263

    • DOI

      10.1203/00006450-201011001-00505

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anti-Fas Gene Therapy Prevents Doxorubicin-induced Acute Cardiotoxicity through Mechanisms Independent of Apoptosis2010

    • Author(s)
      Miyata S, Takemura G, Kosai K, Takahashi T, Esaki M, Li L, Kanamori H, Maruyama R, Goto K, Tsujimoto A, Takeyama T, Kawaguchi T, Ohno T, Nishigaki K, Fujiwara T, Fujiwara H, Minatoguchi S
    • Journal Title

      Am J Pathol

      Volume: 176(2) Issue: 2 Pages: 687-98

    • DOI

      10.2353/ajpath.2010.090222

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neural Development of Methyl-CpG-Binding Protein 2 Null Embryonic Stem Cells : A System for Studying Rett Syndrome.2010

    • Author(s)
      Okabe Y, Takahashi T., et al.
    • Journal Title

      Brain Res

      Volume: 1360 Pages: 17-27

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular genetics and bile acid profiles of 3beta-hydroxy-delta 5-C27-steroid dehydrogenase/isomerase deficiency in 2 Japanise patients.2010

    • Author(s)
      Mizuochi T., Takahashi T., et al.
    • Journal Title

      Pediatr Res

      Volume: 68 Pages: 258-263

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] ヒトES/iPS細胞での再生医療の課題を克服する独自のアデノウイルスベクターと発現技術の開発2012

    • Author(s)
      小戝健一郎、三井薫、王宇清、高橋知之
    • Organizer
      第11回日本再生医療学会総会(横浜)
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] ヒトES/iPS細胞での再生医療の課題を克服する独自のアデノウイルスベクターと発現技術の開発2012

    • Author(s)
      小戝健一郎、三井薫、王宇清、高橋知之
    • Organizer
      第11回日本再生医療学会総会
    • Place of Presentation
      横浜、日本
    • Related Report
      2012 Annual Research Report
  • [Presentation] 再生医療技術によるモデル細胞の樹立と神経分化2011

    • Author(s)
      高橋知之
    • Organizer
      第53回日本小児神経学会総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2011-05-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] RTTモデルES細胞由来神経細胞の電気生理学的解析2011

    • Author(s)
      岡部恭典、久佐賀晃、高橋知之、光益千秋、村井恵良、東英穂、松石豊次郎、小戝健一郎、田中永一郎
    • Organizer
      第88回日本生理学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2011-03-28
    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Presentation] MeCP2遺伝子欠損ES細胞のin vitro分化誘導法によるRett症候群/神経発生の研究システム2011

    • Author(s)
      小戝健一郎、岡部恭典、久佐賀晃、高橋知之、光益千秋、村井恵良、松石豊次郎、田中永一郎
    • Organizer
      第10回日本再生医療学会総会(横浜)
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2011-03-02
    • Related Report
      2012 Final Research Report
  • [Presentation] MeCP2遺伝子欠損ES細胞のin vitro分化誘導法によるRett症候群/神経発生の研究システム2011

    • Author(s)
      小戝健一郎、高橋知之, その他
    • Organizer
      第10回日本再生医療学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2011-03-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] 川崎病急性期における末梢血樹状細胞数に関与するサイトカイン、ケモカイン"Change in Chemokines associated with the number of circulating dendritic cells in acute phase of Kawasaki disease2010

    • Author(s)
      須田憲治、岸本慎太郎、高橋知之、岡村尚昌、横山隆人、寺町陽三、工藤嘉公、家村素史、松石豊次郎
    • Organizer
      第30回日本川崎病学会学術集会(京都)
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2010-10-22
    • Related Report
      2012 Final Research Report
  • [Presentation] Involvement of myeloid dendritic cell in the pathogenesis of acute phase of Kawasaki disease.2010

    • Author(s)
      SudaK,Kishimoto S, Takahashi T,Okamura H, Yasukawa H, Nishino H, Teramachi Y, Itoh S, Yokoyama T, Iemura M, Imaizumi T, MatsushiT.
    • Organizer
      The 74th annual scientific meeting of the Japanese Circulation Society
    • Place of Presentation
      Kyoto,Japan
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] ヒトES/iPS細胞における遺 伝子発現方法2012

    • Inventor(s)
      小戝健一郎、三井薫、高橋知之
    • Industrial Property Rights Holder
      小戝健一郎、三井薫、高橋知之
    • Industrial Property Number
      2012-117128
    • Filing Date
      2012-05-23
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] ヒトES/iPS細胞における遺伝子発現方法2012

    • Inventor(s)
      小戝健一郎、三井薫、高橋知之
    • Industrial Property Rights Holder
      小戝健一郎、三井薫、高橋知之
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-117128
    • Filing Date
      2012-05-23
    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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