Analysis of MeCP2 Function in the CNS

  • Ege T. Kavalali
  • Lisa M. Monteggia
Part of the Research and Perspectives in Neurosciences book series (NEUROSCIENCE)


Mutations in the methyl-CpG-binding protein (MeCP2) have been linked as the causative factor to Rett Syndrome (RTT). The MECP2 gene encodes a DNA binding protein that binds to methylated cytosines in the mammalian genome. The disease-causing mutations found in RTT patients are predicted to result in the loss of function of MeCP2 that then results in genes turned on in an inappropriate manner. Over the past several years, our group has examined the role of MeCP2 in complex behavior as well as neurotransmission. Our behavioral analysis has shown that the forebrain-specific Mecp2 loss-of-function in mice could recapitulate several behavioral and neurological deficits associated with RTT. Interestingly, we could also show that brain region-specific Mecp2 loss-of-function, such as selective knock down of MeCP2 in basolateral amygdala, could trigger a subset of RTT phenotypes such as an increased anxiety-like behavior and deficits in cue-dependent fear conditioning. We have also demonstrated that loss of MeCP2 in neurons results in a decrease in spontaneous excitatory synaptic transmission coupled with an increase in action potential-driven excitatory drive. The combined effort of behavioral and synaptic analysis of MeCP2-associated phenotypes will not only open new avenues for understanding neuronal circuit abnormalities associated with neurodevelopmental disorders but also elucidate potential targets for addressing the pathophysiology of several intractable neuropsychiatric disorders.


Rett Syndrome Excitatory Synaptic Transmission MECP2 Gene Juvenile Mouse MeCP2 Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Department of NeuroscienceUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.Department of PsychiatryUniversity of Texas Southwestern Medical CenterDallasUSA

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