RT Journal Article
SR Electronic
T1 Enhanced anxiety and stress-induced corticosterone release are associated with increased <em>Crh</em> expression in a mouse model of Rett syndrome
JF Proceedings of the National Academy of Sciences
JO Proc Natl Acad Sci USA
FD National Academy of Sciences
SP 18267
OP 18272
DO 10.1073/pnas.0608702103
VO 103
IS 48
A1 McGill, Bryan E.
A1 Bundle, Sharyl F.
A1 Yaylaoglu, Murat B.
A1 Carson, James P.
A1 Thaller, Christina
A1 Zoghbi, Huda Y.
YR 2006
UL http://www.pnas.org/content/103/48/18267.abstract
AB 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 (Mecp2308/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 MeCP2308 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 Mecp2308/Y mouse, thereby providing opportunities for clinical investigation and therapeutic intervention in RTT.