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Study offers new insight into Rett Syndrome

Cambridge, Mass. Rett Syndrome is a major cause of mental retardation in girls. Although researchers have identified the protein involved in the disease, its exact role remains a mystery. Now, a group of researchers from Children's Hospital Boston and Whitehead Institute of Biomedical Research have identified the protein's function, a discovery the scientists say could be the first significant advance in Rett Syndrome research in years.

The study, reported in this week's issue of the journal Science, describes how the protein in question controls gene expression in normal central nervous system cells. Researchers suspect that mutations in the protein impair its ability to regulate genes during a critical stage of brain development.

"We think that this deregulation may be responsible for some of the defects that we see in Rett patients," says Michael Greenberg, director of the Children's Hospital group and a lead author of the study.

A neurological disorder causing mental retardation as well as cerebral-palsy and autism-like symptoms, Rett Syndrome affects one out of approximately 15,000 female babies worldwide. Current therapies, including medications that help prevent seizures, treat some of the symptoms but not the disease.

Researchers have long known that mutations in a protein called MeCP2 somehow cause the disease, but until recently, little was known about how the protein worked. Previous lab experiments demonstrated that MeCP2 binds to genes that have undergone methylation (a fundamental biological process in which the cell disables genes it doesn't use by modifying them with methyl). Like a biological deadbolt, MeCP2 adheres to these methylated genes, further preventing them from ever activating. As a result, scientists theorized that MeCP2 was what they call a "long-range gene repressor."

Rudolf Jaenisch's Whitehead lab has studied this protein for years, demonstrating that when MeCP2 is disabled in mice, the anim
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Contact: Kelli Whitlock
newsroom@wi.mit.edu
617-258-5183
Whitehead Institute for Biomedical Research
30-Oct-2003


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