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Author (up) Okabe, Y.; Kusaga, A.; Takahashi, T.; Mitsumasu, C.; Murai, Y.; Tanaka, E.; Higashi, H.; Matsuishi, T.; Kosai, K.-ichiro url  doi
  Title Neural development of methyl-CpG-binding protein 2 null embryonic stem cells: a system for studying Rett syndrome Type Journal Article
  Year 2010 Publication Brain Research Abbreviated Journal Brain Res  
  Volume 1360 Issue Pages 17-27  
  Keywords Adenoviridae/genetics; Animals; Blotting, Western; Cell Differentiation/physiology; Cells, Cultured; Chromatography, High Pressure Liquid; Clone Cells; Dopamine/physiology; Electrophysiological Phenomena; Embryonic Stem Cells/*physiology; Genetic Vectors; Glial Fibrillary Acidic Protein/metabolism; Immunohistochemistry; Methyl-CpG-Binding Protein 2/*genetics/*physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Neural Stem Cells/*physiology; Neurogenesis/physiology; Neuroglia/physiology; Neurons/physiology; Rett Syndrome/*genetics/*pathology; Reverse Transcriptase Polymerase Chain Reaction  
  Abstract Mutations in methyl-CpG-binding protein 2 (MeCP2) gene cause the neurodevelopmental disorder Rett syndrome (RTT). Here, we describe a new experimental system that efficiently elucidates the role of MeCP2 in neural development. MeCP2-null and control ES cells were generated by adenoviral conditional targeting and examined for maintenance of the undifferentiated ES cell state, neurogenesis, and gliogenesis during in vitro differentiation. In addition, dopamine release and electrophysiological features of neurons differentiated from these ES cells were examined. Loss of MeCP2 did not affect undifferentiated ES cell colony morphology and growth, or the timing or efficiency of neural stem cell differentiation into Nestin-, TuJ- or TH-positive neurons. In contrast, gliogenesis was drastically accelerated by MeCP2 deficiency. Dopamine production and release in response to a depolarizing stimulus in MeCP2-null ES-derived dopaminergic neurons was intact. However, MeCP2-null differentiated neurons showed significantly smaller voltage-dependent Na(+) currents and A-type K(+) currents, suggesting incomplete maturation. Thus, MeCP2 is not essential for maintenance of the undifferentiated ES cell state, neurogenesis, or dopaminergic function; rather, it is principally involved in inhibiting gliogenesis. Altered neuronal maturity may indirectly result from abnormal glial development and may underlie the pathogenesis of RTT. These data contribute to a better understanding of the developmental roles of MeCP2 and the pathogenesis of RTT.  
  Address Division of Gene Therapy and Regenerative Medicine, Kurume University, Kurume, Japan  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0006-8993 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:20816763 Approved no  
  Call Number refbase @ user @ Serial 17003  
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