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2 genes affect anxiety, behavior in mice with too much MeCP2
Date:1/8/2012

genes are the culprits in mediating anxiety and social behavioral problems is surprising," said Dr. Huda Zoghbi, professor of molecular and human genetics, neurology, neuroscience, and pediatrics at BCM and director of the NRI. She is the corresponding author of the report and a Howard Hughes Medical Institute Investigator.

Patients with MeCP2 duplication disorder have a duplication in chromosomes that span both the MECP2 gene and another called IRAK1. But with this new study, it is now clear that excess MeCP2 accounts for the neuropsychiatric symptoms.

In mice, doubled MeCP2 levels caused both anxiety and autism-like behaviors and altered the expression of several hundred genes. Of these, two genes Crh and Oprm1, are implicated in anxiety and social behavior, said Samaco.

"Then, when we reduced the levels of Crh, we saw reduced anxiety," he said. "When we reduced levels of Oprm1, we improved the social behavior problems."

This finding is important because it shows that tweaking the expression of genes that the protein affects, rather than trying to adjust the levels of the finicky MeCP2 protein itself, can modify symptoms of MeCP2 disorders.

In fact, Samaco also reduced levels of the protein that is a cellular receptor for Crh, both through molecular means and with the use of a drug, and found that anxiety levels also went down. That could provide another means of dealing with anxiety associated with the duplication syndrome.


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Contact: Graciela Gutierrez
ggutierr@bcm.edu
713-798-4710
Baylor College of Medicine
Source:Eurekalert

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