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Convulsions in worms mimic epileptic seizures

Researchers at the University of Alabama have found a way to mimic epileptic seizures in the tiny roundworm C. elegans. The finding could make the worm a powerful model for unraveling the molecular regulation of epilepsy, a condition that affects two percent of the population.

Guy A. Caldwell, coordinator of the Howard Hughes Medical Institute's (HHMI) Undergraduate Research Intern Program and assistant professor of biological sciences at the University of Alabama, led a research team that included Kim A. Caldwell, assistant professor of biological sciences and director of the university's HHMI-sponsored Rural Science Scholars Program; Shelli N. Williams, a Ph.D. student; and two HHMI undergraduate research interns, Cody J. Locke and Andrea L. Braden. They studied worms with a mutation in the LIS1 gene. In its human form, the gene has been linked to a rare birth defect called lissencephaly, which affects one out of every 30,000 children born. In children with lissencephaly, the normally wrinkled surface of the brain's cortex is smooth. They also have mental retardation and severe epilepsy, the causes of which are not well understood.

The team traced the mutation's effect on specific neurons in the simple nervous system of the 1-millimeter roundworm and published their findings in the September 15, 2004 issue of the journal Human Molecular Genetics, published online August 31.

"The human brain has 100 billion neurons, whereas the worm has only 302. We know each type of neuron and how they connect to each other," Caldwell explained. "We knew that LIS1 is highly expressed in the nervous system, so we wanted to see if there was a way to use C. elegans to understand and simplify the complexities of brain disease."

The team identified a mutation in the LIS1 gene that causes the encoded protein to be only one-fourth the length of the normal protein. The mutation was lethal to 70 percent of the mutant worms. The team tested the survivors
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Contact: Jennifer Donovan
donovanj@hhmi.org
301-215-8859
Howard Hughes Medical Institute
1-Sep-2004


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