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Preclinical work shows how one gene causes severe mental retardation
Date:5/10/2009

Durham, N.C., and Chapel Hill, N.C. -- Researchers at Duke University Medical Center and the University of North Carolina have discovered in mice how a single disrupted gene can cause a form of severe mental retardation known as Angelman syndrome.

In a study published in the journal Nature Neuroscience, they found that the gene, UBE3A, is needed so that neurons in the brain can form and adjust their connections to other neurons for storing sensory information. They also made a promising discovery: When the mice were deprived of sensory stimulation, the brain connections could be recovered, a finding that indicated a pharmaceutical or behavioral treatment might be possible in the future.

The scientists undertook this project because of the developmental-onset period seen in Angelman syndrome, typically when children are between one and two years old. It is during this time in humans that the cortex, the sheet of convoluted folds at the surface of the brain, undergoes profound rearrangements driven by sensory experiences the experience of seeing reorganizes the visual cortex, for example, during the same time period when the deficits are becoming obvious in Angelman syndrome, part of the autism spectrum of disorders.

"We wanted to look at an animal model to learn if this experience-dependent reorganization of the cortex was abnormal in animals that were missing the gene," said Michael Ehlers, M.D., Ph.D., a Duke professor of neurobiology and co-senior author of the study. "We looked at the visual cortex, because in this well-studied model, we could precisely control the sensory stimulus and study the mice in the light or the dark. We speculated that similar deficits may be happening in areas of the cortex that are important for language, cognition and emotion, all of which are quite abnormal in Angelman syndrome patients."

The authors found that brains cells in Angelman syndrome mice lacked the ability to appropr
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Contact: Mary Jane Gore
mary.gore@duke.edu
919-660-1309
Duke University Medical Center
Source:Eurekalert

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