Joseph Gleeson, M.D., Director of the Neurogenetics Laboratory at the UCSD School of Medicine, and his team developed a mouse model for the severe brain disorder in newborn children, also known as "smooth brain," reports Newswise.
"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."
Gleeson and his team had already shown that mutations in the doublecortin gene are responsible for nearly 20 percent of lissencephaly cases in humans. However, researchers had not been able to prove that a similar condition in laboratory mice resulted from a genetic alteration of the doublecortin gene, reports Newswise.
USCD researchers removed both the doublecortin gene and a closely related gene from the mouse. After both genes were taken out, the lab mice displayed characteristics similar to those with human cases of lissencephaly.
"This study shows that brain development in mice is less susceptible to genetic deletions than in humans, because there is a redundant mechanism that fills in when just one gene is missing" says Gleeson.
He adds, "The human brain is one of the most complex structures we know of, and evolution has been working hard to make the human brain over the past million years. It is not surprising that the human brain is more susceptible to genetic variation than the brain of a laboratory mouse."
The study is published in the Jan. 5, 2006 issue of the journal Neuron.
