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New findings may lead to treatment for anxiety in Rett Syndrome

The classic form of Rett Syndrome (RTT) shows us a child who is the picture of anxiety: she wrings her hands, hyperventilates, trembles. The sinister progression of the disorder, which usually begins to manifest between the ages of 6-18 months, includes loss of acquired skills, speech and mobility, sometimes an autistic-like withdrawal, sometimes months of inconsolable crying. A majority of girls with RTT, which is caused by mutations in the gene MECP2, display elevated stress hormones measured by urinary cortisol levels. New studies may shed light on whether much of the anxiety of these children is a response to the subjective experience of RTT, or is an intrinsic aspect of the disorder.

The lab of Huda Zoghbi at Baylor College of Medicine has been studying anxiety in their mouse model of the syndrome. These MeCP2308 mice, so called because they bear a mutant version of the MeCP2 protein that is truncated prematurely (at amino acid 308), have numerous characteristics that mimic human RTT. They appear to be healthy early on in life, but within several weeks of birth develop tremors, spasticity, seizures, and begin to display impairments in social behavior and cognitive skills. They also show signs of anxiety: they huddle in closed spaces rather than curiously exploring new areas, they avoid spending time with other animals, they tremble noticeably when being handled by the gentlest of researchers. And, as the Zoghbi lab now reports in The Proceedings of the National Academy of Sciences, the mice produce high levels of corticosterone, the mouse equivalent of the human stress hormone.

What causes the mice to be so stressed? Because MECP2 controls the expression of other genes, mutations in the protein that disrupt its normal function should allow misexpression of target genes. Thus far, five targets of MeCP2 activity have been identified, though the precise role any of them play in the RTT phenotype remains unclear. But the combination of a
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Contact: Monica Coenraads
monica@rsrf.org
203-243-5733
Rett Syndrome Research Foundation
13-Nov-2006


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