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PMID:22231481
| Citation |
Samaco, RC, Mandel-Brehm, C, McGraw, CM, Shaw, CA, McGill, BE and Zoghbi, HY (2012) Crh and Oprm1 mediate anxiety-related behavior and social approach in a mouse model of MECP2 duplication syndrome. Nat. Genet. 44:206-11 |
|---|---|
| Abstract |
Genomic duplications spanning Xq28 are associated with a spectrum of phenotypes, including anxiety and autism. The minimal region shared among affected individuals includes MECP2 and IRAK1, although it is unclear which gene when overexpressed causes anxiety and social behavior deficits. We report that doubling MECP2 levels causes heightened anxiety and autism-like features in mice and alters the expression of genes that influence anxiety and social behavior, such as Crh and Oprm1. To test the hypothesis that alterations in these two genes contribute to heightened anxiety and social behavior deficits, we analyzed MECP2 duplication mice (MECP2-TG1) that have reduced Crh and Oprm1 expression. In MECP2-TG1 animals, reducing the levels of Crh or its receptor, Crhr1, suppressed anxiety-like behavior; in contrast, reducing Oprm1 expression improved abnormal social behavior. These data indicate that increased MeCP2 levels affect molecular pathways underlying anxiety and social behavior and provide new insight into potential therapies for MECP2-related disorders. |
| Links |
PubMed PMC3267865 Online version:10.1038/ng.1066 |
| Keywords |
Animals; Anxiety/blood; Anxiety/genetics; Behavior, Animal; Corticosterone/blood; Corticotropin-Releasing Hormone/genetics; Disease Models, Animal; Female; Gene Duplication; Male; Methyl-CpG-Binding Protein 2/genetics; Mice; Mice, Inbred C57BL; Mutation; Receptors, Opioid, mu/genetics; Social Behavior; Syndrome |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
involved_in |
GO:0035176: social behavior |
ECO:0000316: genetic interaction evidence used in manual assertion |
UniProtKB:Q9Z2D6 |
P |
Seeded From UniProt |
complete | ||
| GO:0035176: social behavior |
ECO:0000316: |
UniProtKB:Q9Z2D6
|
P |
Figure 6a shows that the mice who have already received social deficits through mutation are able to regain social behavior function through reducing the Oprm1 gene. This graph shows wild type mice having the highest amount of socialization time and the mutated mice with the most reduction of the Oprm1 gene regaining a lot of their lost socialization skills. |
complete | |||
See also
References
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