Symptomatic male mice have altered hippocampal NMDA Selleckchem CDK inhibitor receptor expression and impairments in LTP and LTD ( Asaka et al., 2006). Male mutant mice also display deficits in cued fear conditioning, while mutant mice of both sexes display deficits in object recognition and altered anxiety ( Stearns et al., 2007). The MeCP2 null mice generated by the Bird and

Jaenisch laboratories display an early onset of symptoms and short life span that differentiates them from classic Rett syndrome and limits the analysis of symptoms. Two groups have developed models that attempted to address these limitations. The Zoghbi group generated the mutant mouse model MeCP2308/Y, possessing a premature stop after codon 308, where mutations have been frequently indentified in humans with Rett syndrome. These mice exhibit a milder phenotype, www.selleckchem.com/products/umi-77.html presumably because the truncated protein retains partial function, characterized by impaired motor function, reduced activity, stereotypic forelimb-clasping movement, and abnormal social interactions (Moretti et al., 2005). MeCP2308/Y mice also display

impaired LTP, increased basal synaptic transmission, and deficits in the induction of LTD, as well as corresponding disruptions in spatial memory, contextual fear conditioning, and long-term social memory (Moretti et al., 2006). Importantly, these mice possess hyperacetylation of H3 (Shahbazian et al., 2002). The Tam group generated another line of MeCP2 null mice (Mecp2tm1Tam) with a deletion of the methyl-binding domain. Behavioral testing of these mice revealed deficits in cerebellar learning and impairments in both cued and contextual fear conditioning and contextual association (Pelka et al., 2006). In Dichloromethane dehalogenase a collaborative effort, the Zoghbi and Sweatt laboratories showed that MeCP2-deficient animals have deficits in spatial learning, contextual fear conditioning, and LTP deficits (Moretti et al., 2006). Moreover, they also showed that overexpression of MeCP2 resulted in enhanced

fear conditioning and enhanced LTP (Collins et al., 2004). Since Rett syndrome is caused by mutations in MeCP2, enhancing MeCP2 levels could therefore be a therapeutic option. Overall, these findings strongly support the idea that MeCP2 might be involved in regulation of LTP and hippocampal-dependent memory formation. Rett syndrome has classically been viewed as a neurodevelopmental disorder, the underlying genetic basis of which is mutation/deletion of the MeCP2 gene and resultant disruption of normal MeCP2 function during prenatal and early postnatal development. This model is consistent with the fact that the mutated gene product is present throughout development. However, the mutant gene product is also present in the fully developed adult CNS.