Mecp2 deficiency is associated with learning and cognitive deficits and altered gene activity in the hippocampal region of mice

Brain. 2006 Apr;129(Pt 4):887-98. doi: 10.1093/brain/awl022. Epub 2006 Feb 8.


Rett syndrome (RTT) is a debilitating neurological condition associated with mutations in the X-linked MECP2 gene, where apparently normal development is seen prior to the onset of cognitive and motor deterioration at 6-18 months of life. A targeted deletion of the methyl-CpG-binding domain (MBD) coding region and disruption of mRNA splicing was introduced in the mouse, resulting in a complete loss of Mecp2 transcripts and protein. Postnatal comparison of XO and XY mutant Mecp2 allele-containing null mice revealed similar effects on mouse growth and viability, suggesting that phenotypic manifestations are not modulated by the Y-chromosome. Further assessment of Mecp2-null XY mice highlighted cerebellar and hippocampal/amygdala-based learning deficits in addition to reduced motor dexterity and decreased anxiety levels. Brain tissues containing the hippocampal formation of XY Mecp2-null mice also displayed significant changes in genetic activity, which are related to the severity of the mutant phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety
  • Conditioning, Classical
  • Disease Progression
  • Fear
  • Gene Expression Regulation
  • Gene Targeting / methods
  • Hippocampus / metabolism*
  • Learning
  • Male
  • Methyl-CpG-Binding Protein 2 / deficiency*
  • Methyl-CpG-Binding Protein 2 / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Motor Activity
  • Phenotype
  • Rett Syndrome / genetics
  • Rett Syndrome / metabolism*
  • Rett Syndrome / physiopathology
  • Rett Syndrome / psychology
  • Y Chromosome / physiology


  • Methyl-CpG-Binding Protein 2