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Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18267-72. Epub 2006 Nov 15.

Enhanced anxiety and stress-induced corticosterone release are associated with increased Crh expression in a mouse model of Rett syndrome.

Author information

1
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.

Abstract

Rett syndrome (RTT), a postnatal neurodevelopmental disorder, is caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Children with RTT display cognitive and motor abnormalities as well as autistic features. We studied mice bearing a truncated Mecp2 allele (Mecp2(308/Y) mice) and found evidence of increased anxiety-like behavior and an abnormal stress response as evidenced by elevated serum corticosterone levels. We found increased corticotropin-releasing hormone (Crh) gene expression in the paraventricular nucleus of the hypothalamus, the central amygdala, and the bed nucleus of the stria terminalis. Finally, we discovered that MeCP2 binds the Crh promoter, which is enriched for methylated CpG dinucleotides. In contrast, the MeCP2(308) protein was not detected at the Crh promoter. This study identifies Crh as a target of MeCP2 and implicates Crh overexpression in the development of specific features of the Mecp2(308/Y) mouse, thereby providing opportunities for clinical investigation and therapeutic intervention in RTT.

PMID:
17108082
PMCID:
PMC1636379
DOI:
10.1073/pnas.0608702103
[Indexed for MEDLINE]
Free PMC Article

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