UCSD team creates model for genetic brai...( Researchers at the University of Califo...),Health

Joseph Gleeson, M.D., Director of the Neurogenetics Laboratory at the UCSD School of Medicine and associate professor in the Department of Neurosciences, and his research team have developed a mouse model for a severe brain disorder in newborn children called lissencephaly, or "smooth brain."

"This is the first study to establish a link between the human and mouse disease that clearly shows we can model this condition in the lab," said Gleeson. "This study will allow us to begin to better understand what goes wrong in lissencephaly, and to use this mouse to figure out why children with this disease develop seizures and mental retardation."

It had been known that children with a genetic alteration in a gene called doublecortin suffer from epilepsy and mental retardation due to a defect in how the neuronal stem cells are positioned within the cerebral cortex. In the normal brain, neurons are born adjacent to fluid-filled cavities deep within the developing brain during the third and fourth month of gestation. Then they must migrate to reach their proper position within the six-layered cortex. When this migration is defective and neurons stop short of their proper destination, there is an absence of the normal grooves and ridges that characterize the brain in high mammals, including mice. Only four, instead of six, layers of cortex are formed, and the cerebral cortex of these patients lacks most or all of the hills and valleys of the normal human brain.

Gleeson and colleagues previously showed that mutations in the doublecortin gene account for nearly 20 percent of lissencephaly cases in humans. However, previous research by his lab and others yielded conflicting results about the n
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Contact: Debra Kain
ddkain@ucsd.edu
619-543-6163
University of California - San Diego
4-Jan-2006