Scientists Recreate Autism With One Gene

March 21, 2011— -- Autism symptoms have been replicated in mice using one gene mutation, one of the first so-called single-gene knockouts that scientists say puts them another step closer to understanding a genetic link to autism, researchers at Duke University reported.

Their findings were published Sunday in the journal Nature.

"This is an exciting additional edge piece in a jigsaw puzzle," said Dr. Thomas Insel, director of the National Institutes of Health's National Institute of Mental Health, who was not involved in the study. "By following the thread of a genetic reason that you know is associated with autism, you see what else is changing in the brain."

Scientists examining genetic traits or environmental exposures that can contribute to autism have previously replicated behavioral symptoms of autism in mice. But these mouse models of autism replicated only a few specific behavioral traits associated with autism.

This new model, according to researchers, used a known gene mutation associated with autism -- called the SHANK3 gene mutation -- to replicate a wider range of behaviors that include impaired social interaction and repetitive behaviors.

Scientists have struggled for years to find effective medical treatments for autism, mainly because they have been unable to understand the pathways in the brain that cause the disorder.

"We've known for about three decades that there are common gene variants associated with autism," Insel said. "We didn't have a way to chase down the genes and understand how these genes are altering brain development to bring on autism."

Previous studies suggest that SHANK3 gene mutation is one of a series of rare genetic mutations that are linked to autism. The SHANK3 gene mutation has been identified in nearly 1 percent of children with autism. However nearly 16 percent of children with autism have been found to have some type of gene mutation. Earlier studies, however, do not pinpoint the exact role the mutations played in the disorder.

"Having an animal model that can teach us more about how a specific gene mutation is correlated with behavior is critically important to our understanding of the overall biology of autism," said Andy Shih, vice president of scientific affairs at the nonprofit Autism Speaks.

'Big Step' Toward Understanding Autism

The current findings may offer some insight in the relationship between SHANK3 mutations and the characteristic traits of autism. Some experts say it's hard to tell whether insights that will be gained from the SHANK3 mutation will translate to the other genetic mutations that are associated with autism.

"There may be some shared mechanisms and there may be some specific to SHANK3 that may not be generalizable," said Dr. Shlomo Shinnar, director of the comprehensive epilepsy management center at Montefiore Medical Center in New York City.

Still, Insel of the National Institutes of Health said, so-called single-gene knockouts such as this have been one of the first instrumental steps in better understanding the mechanism of many now manageable conditions in humans, including heart disease and hypertension.

"This is a big step," he said. "But we need a lot more big steps to get to finding early diagnostic and medical treatments.

"It doesn't yet tell us where a new treatment or diagnosis will be. But this is part of the process."