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

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...

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Bibliographic Details
Published in:The Journal of neuroscience 2009-04, Vol.29 (13), p.4218-4227
Main Authors: Adachi, Megumi, Autry, Anita E, Covington, Herb E., III, Monteggia, Lisa M
Format: Article
Language:English
Subjects:
Amygdala - drug effects
Amygdala - metabolism
Amygdala - pathology
Animals
Anxiety - etiology
Anxiety - pathology
Anxiety - physiopathology
Conditioning (Psychology) - drug effects
Conditioning (Psychology) - physiology
Disease Models, Animal
Enzyme Inhibitors - administration & dosage
Fear - psychology
Green Fluorescent Proteins - genetics
Histone Deacetylases - genetics
Histone Deacetylases - metabolism
Hydroxamic Acids - administration & dosage
Interpersonal Relations
Male
Maze Learning - drug effects
Maze Learning - physiology
Methyl-CpG-Binding Protein 2 - deficiency
Methyl-CpG-Binding Protein 2 - genetics
Methyl-CpG-Binding Protein 2 - metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Motor Activity - drug effects
Motor Activity - genetics
Mutation
Neurons - metabolism
Pain Threshold - drug effects
Pain Threshold - physiology
Recombinases - genetics
Rett Syndrome - complications
Rett Syndrome - pathology
Time Factors
Transcription, Genetic - drug effects
Transcription, Genetic - genetics
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Summary: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.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.4225-08.2009