The study of impaired autonomic nerve system in Rett syndrome model mice and ES/iPS cells derived from them

• Project/Area Number: 26860832
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Kurume University
• Principal Investigator: HARA MUNETSUGU 久留米大学, 医学部, 助教 (30389283)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: Rett症候群 / 心臓 / MeCP2 / レット症候群

Outline of Final Research Achievements

Rett Syndrome (RTT) is a neurodevelopmental disorder predominantly affecting females. Most cases of RTT are caused by de novo mutations in methyl-CpG binding protein 2 (MeCP2) gene on X chromosome. Several studies found the prolonged QT interval and lethal cardiac arrhythmias in RTT patients and Mecp2-deficient animal disease models. In this study, we investigated the contribution of MeCP2 to cardiac development, structure, and function using an in vitro ES cell model system and an in vivo mouse model for RTT. Our results demonstrate that MeCP2 deficiency impairs the development and further cardiac differentiation of cardiac progenitor cells. We also show that MeCP2 is involved in maintaining normal cardiac gene expression and cardiomyocyte structure in the adult mouse heart. Moreover, we found that MeCP2 may regulate the gene expression of Tbx5, a transcriptional factor essential to cardiac development and function.

Research Products

• [Journal Article] Disturbance of cardiac gene expression and cardiomyocyte structure predisposes Mecp2-null mice to arrhythmias. (2015)
  • Author(s): Hara M, Takahashi T, Mistumasu C, Igata S, Takano M, Minami T, Yasukawa H, Okayama S, Nakamura K, Okabe Y, Tanaka E, Takemura G, Kosai K, Yamashita Y, Matsuishi T.
  • Journal Title: Sci Rep Volume: 5 Issue: 1 Pages: 11204-11204
  • DOI: 10.1038/srep11204
  • Peer Reviewed / Open Access
• [Journal Article] De novo SHANK3 mutation causes a female patient with Rett syndrome like phenotype. (2015)
  • Author(s): Hara M, Ohba C, Yamashita Y, Saitsu H, Matsumoto N, Matsuishi T.
  • Journal Title: J Med Genet Part A Volume: 167(7) Issue: 7 Pages: 1593-1596
  • DOI: 10.1002/ajmg.a.36775
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] De novo KCNT1 mutations in early-onset epileptic encephalopathy. (2015)
  • Author(s): Ohba C, Kato M, Takahashi N, Osaka H, Shiihara T, Tohyama J, Nabatame S, Azuma J, Fujii Y, Hara M, Tsurusawa R, Inoue T, Ogata R, Watanabe Y, Togashi N, Kodera H, Nakashima M, Tsurusaki Y, Miyake N, Tanaka F, Saitsu H, Matsumoto N.
  • Journal Title: Epilepsia Volume: 56(9) Issue: 9
  • DOI: 10.1111/epi.13072
  • Peer Reviewed / Open Access
• [Journal Article] Clinically mild encephalitis with a reversible splenial lesion (MERS) after mumps vaccination. (2015)
  • Author(s): Takanashi J, Shiihara T, Hasegawa T, Takayanagi M, Hara M, Okumura A, Mizuguchi M.
  • Journal Title: J Neurol Sci Volume: 349(1-2) Issue: 1-2 Pages: 226-228
  • DOI: 10.1016/j.jns.2014.12.019
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] serial 18FDG-PET study of a patient with SSPE who had good prognosis by combination therapy with interferon alpha and ribavirin (2014)
  • Author(s): Ohya T, Yamashita Y, Shibuya I, Hara M, Nagamitsu S, Kaida H, Kurata S, Ishibashi M, Matsuishi T
  • Journal Title: Brain Dev Volume: in press Issue: 4 Pages: 41-45
  • DOI: 10.1016/j.ejpn.2014.03.001
  • Peer Reviewed
• [Journal Article] Relation between circulating levels of GH, IGF-1, ghrelin and somatic growth in Rett syndrome (2013)
  • Author(s): Hara M, Nishi Y, Yamashita Y, Hirata R, Takahashi S, Nagamitsu SI, Hosoda H, Kangawa K, Kojima M, Matsuishi T
  • Journal Title: Brain Dev Volume: 36 Issue: 9 Pages: 794-800
  • DOI: 10.1016/j.braindev.2013.11.007
  • Peer Reviewed
• [Presentation] Analysis of cardiac arrthymias and gene expression in MeCP2-null mice. (2014)
  • Author(s): Hara M, Takahashi T, Mitsumasu C, Igata S, Takano M, Okabe Y, Tanaka E, Matsuishi T.
  • Organizer: 13th Rett syndrome Symposium.
  • Place of Presentation: Chantilly, VA, USA.
  • Year and Date: 2014-06-24 – 2014-06-26