MeCP2-Mediated Transcription Repression in the Basolateral Amygdala May Underlie Heightened Anxiety in a Mouse Model of Rett Syndrome

作者：Adachi Megumi; Autry Anita E; Covington Herb E III; Monteggia Lisa M^*

来源：Journal of Neuroscience, 2009, 29(13): 4218-4227.

DOI：10.1523/JNEUROSCI.4225-08.2009

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder that results from loss of function mutations in the methyl-CpG binding protein 2 (MECP2) gene. Using viral-mediated basolateral amygdala (BLA)-specific deletion of Mecp2 in mice, we show that intact Mecp2 function is required for normal anxiety behavior as well as some types of learning and memory. To examine whether these behavioral deficits are the result of impaired transcriptional repression, because Mecp2 is believed to act as a transcriptional repressor in complex with histone deacetylases (HDACs), we infused a HDAC inhibitor chronically into the BLA of wild-type mice. We found that HDAC inhibition produces behavioral deficits similar to those observed after the deletion of Mecp2 in the BLA. These results suggest a key role for Mecp2 as a transcriptional repressor in the BLA in mediating behavioral features of RTT.

• 出版日期2009-4-1