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PMID: 17108082 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 103 ·No. 48 ·2006-11-28 ·Pages 18267-72

McGill BE, Bundle SF, Yaylaoglu MB, Carson JP, Thaller C, Zoghbi HY

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.

MeSH Terms
Animals Anxiety/metabolism Behavior, Animal Corticosterone/metabolism Corticotropin-Releasing Hormone/genetics,metabolism Disease Models, Animal Female Gene Expression Regulation Male Methyl-CpG-Binding Protein 2/genetics,metabolism Methylation Mice Mice, Transgenic Mutation/genetics Promoter Regions, Genetic/genetics Protein Binding Rett Syndrome/metabolism Stress, Physiological/metabolism Transcription, Genetic/genetics Tyrosine/genetics
Chemicals
Methyl-CpG-Binding Protein 2 Tyrosine Corticotropin-Releasing Hormone Corticosterone
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
McGill Bryan E
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
Bundle Sharyl F
Yaylaoglu Murat B
Carson James P
Thaller Christina
Zoghbi Huda Y
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0608702103
Published
2006-11-28
Epub
2006-00-15
Pages
18267-72
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1636379
Subset
IM
Grants
NICHD NIH HHS · R01HD40301 · United States
NLM NIH HHS · 5T15LM07093 · United States
NIMH NIH HHS · F30 MH068996 · United States
NCRR NIH HHS · P41 RR0250 · United States
NICHD NIH HHS · P30 HD024064 · United States
NCRR NIH HHS · P41 RR002250 · United States
NLM NIH HHS · T15 LM007093 · United States
NICHD NIH HHS · P01 HD040301 · United States
External Links
PubMed source DOI: 10.1073/pnas.0608702103 PMC Full Text View journal details
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