Reversal of neurological defects in a mouse model of Rett syndrome

Science. 2007 Feb 23;315(5815):1143-7. doi: 10.1126/science.1138389. Epub 2007 Feb 8.


Rett syndrome is an autism spectrum disorder caused by mosaic expression of mutant copies of the X-linked MECP2 gene in neurons. However, neurons do not die, which suggests that this is not a neurodegenerative disorder. An important question for future therapeutic approaches to this and related disorders concerns phenotypic reversibility. Can viable but defective neurons be repaired, or is the damage done during development without normal MeCP2 irrevocable? Using a mouse model, we demonstrate robust phenotypic reversal, as activation of MeCP2 expression leads to striking loss of advanced neurological symptoms in both immature and mature adult animals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Chimera
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation*
  • Gene Targeting
  • Long-Term Potentiation
  • Male
  • Methyl-CpG-Binding Protein 2 / genetics*
  • Methyl-CpG-Binding Protein 2 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neurons / physiology*
  • Phenotype
  • Rett Syndrome / genetics*
  • Rett Syndrome / physiopathology
  • Rett Syndrome / therapy*
  • Synaptic Transmission
  • Tamoxifen / pharmacology
  • Transgenes


  • Mecp2 protein, mouse
  • Methyl-CpG-Binding Protein 2
  • Tamoxifen