Original articlePostnatal Loss of Methyl-CpG Binding Protein 2 in the Forebrain is Sufficient to Mediate Behavioral Aspects of Rett Syndrome in Mice
Section snippets
Generation of MeCP2 Conditional Knockout Mice
The CaMKII-Cre93 line was on a mixed 129/BALBC background that was back-crossed to a C57BL/6 line. The floxed MeCP2 was also on a similar mixed background and was back-crossed to C57BL/6 mice. Male CaMKII-Cre93 mice were crossed with female floxed MeCP2 mice, and the resulting bigenic mice exhibited no obvious initial phenotypic difference (Chen et al 2001). All experiments were performed on littermates derived from this mating paradigm to ensure analysis by matched control (CTL) mice and to
Conditional MeCP2 KO Mice Show a Selective Deletion of MeCP2 in Forebrain Regions
To determine the regional distribution of the MeCP2 deletion in the conditional KO mice compared with CTL littermates, we used fluorescent immunohistochemistry. In all animals, the MeCP2 staining was localized to the neuronal nuclei. The conditional MeCP2 KO mice showed a clear reduction in MeCP2 staining in the prefrontal cortex, striatum, nucleus accumbens, hippocampus, and amygdala compared with the CTL littermates (Figure 1A); however, the level of MeCP2 in the habenula was unchanged
Discussion
The results presented in this study show that conditional MeCP2 KO mice display behavioral deficits that are characteristic of many features of RTT. These conditional MeCP2 KO mice have motor coordination deficits, increased anxiety, and impaired social interactions with other mice. These mice, however, have normal locomotor activity and unimpaired context-dependent fear conditioning, suggesting that the behavioral deficits observed are the result of loss of MeCP2 function in postnatal brain
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