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Model for angelman syndrome developed by University of Texas at Austin biologists
Date:8/14/2008

AUSTIN, TexasA model for studying the genetics of Angelman syndrome, a neurological disorder that causes mental retardation and other symptoms in one out of 15,000 births, has been developed by biologists at The University of Texas at Austin.

Their research demonstrates that when a particular fruit fly gene, dube3a, is altered, the mutant flies show behavioral dysfunctions similar to those experienced by humans whose UBE3A gene doesn't function normally.

The work, led by Yaning Wu and Janice Fischer of the Section of Molecular Cell and Developmental Biology, is described in PNAS Early Edition online this week (Aug. 11-15), and will appear in the print version of the Proceedings of the National Academy of Sciences later this month.

"People inherit Angelman syndrome as a mutant UBE3A gene that does not make UBE3A protein," says Fischer, a professor in the Institute for Cellular and Molecular Biology.

The UBE3A protein is an enzyme that attaches a small protein called ubiquitin to other proteins. Ubiquitin attachment signals that the tagged protein needs to be degraded.

"The simplest explanation for the disease biochemistry is that when UBE3A is not around to do its job, its substrates aren't being degraded like they should be, and these proteins build up and interfere with brain functions," Fischer says.

The symptoms of Angelman syndrome in humans include severe mental retardation, epileptic seizures and sleep disturbances.

The work Wu, Fischer and their collaborators have done over the last six years has involved engineering fruit flies with the appropriate mutations in their genes and also particular control transgenes.

The researchers ran the mutant flies through a series of tests, comparing their performances to control groups of flies whose dube3a genes functioned normally. Among other results, the mutant flies weren't able to climb as well up the sides of plastic containers, weren't
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Contact: Dr. Janice Fischer
jaf@mail.utexas.edu
512-471-5831
University of Texas at Austin
Source:Eurekalert

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