Rett syndrome treatment in mouse models: searching for effective targets and strategies

Neuropharmacology. 2013 May:68:106-15. doi: 10.1016/j.neuropharm.2012.08.010. Epub 2012 Aug 23.

Abstract

Rett syndrome (RTT) is a pervasive developmental disorder, primarily affecting girls with a prevalence of 1 in every 10,000 births; it represents the second most common cause of intellectual disability in females. Mutations in the gene encoding methyl-CpG-binding protein 2 (MECP2) have been identified as clear etiological factors in more than 90% of classical RTT cases. Whereas the mechanisms leading to the severe, progressive and specific neurological dysfunctions when this gene is mutated still remain to be elucidated, a series of different mouse models have been generated, bearing different Mecp2 mutation. Neurobehavioural analysis in these mouse lines have been carried out and phenotyping analysis can be now utilised to preclinically evaluate the effects of potential RTT treatments. This review summarizes the different results achieved in this research field taking into account different key targets identified to ameliorate RTT phenotype in mouse models, including those not directly downstream of MeCP2 and those limited to the early phases of postnatal development. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anxiety / genetics
  • Choline / pharmacology
  • Choline / therapeutic use
  • Cognition / drug effects
  • Cognition / physiology
  • Disease Models, Animal*
  • Genotype
  • Methyl-CpG-Binding Protein 2 / genetics
  • Mice
  • Motor Activity / drug effects
  • Motor Activity / genetics
  • Phenotype
  • Rett Syndrome / drug therapy*
  • Rett Syndrome / genetics

Substances

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