'Rain Man' mice provide model for autism

September 07, 2007

DALLAS - Sept. 7, 2007 - Mice containing a mutated human gene implicated in autism exhibit the poor social skills but increased intelligence akin to the title character's traits in the movie "Rain Man," researchers at UT Southwestern Medical Center have found.

The researchers' study also shows how the mutation affects nerve function and provides an animal model that might allow further study of the debilitating condition.

"It's an attempt to replicate, as best we can, a complicated disease that has as a symptom an inability to use language effectively," said Dr. Thomas Südhof, chairman of neuroscience and senior author of the study, which appears online in Science Express and will be published later in Science.

"Any model we make will only be an approximation of the human condition," he cautioned.

Autism spectrum disorders cover a wide span of conditions and symptoms, from severe mental retardation to mild social impairment. In general, people with autism have problems with social interactions, such as maintaining eye contact or reading body language. They may also exhibit stereotypical behavior, such as being obsessed with lining up objects. In the movie "Rain Man," the title character was unable to form social bonds and became distressed when his normal routine was disrupted, yet he could perform exceptional mental mathematics.

About 1.5 million people in the United States have autism spectrum disorders, with boys affected more often than girls.

Some cases of autism are genetically linked and have been associated with mutations that affect molecules called neuroligins, which link nerve cells together.

In the latest study, the researchers introduced a mutated human form of the neuroligin-3 molecule into mice. They then tested the animals' social interactions by exposing them to an unknown mouse in a cage. The genetically engineered mice spent less time near the strange mouse than their normal littermates and preferred to spend time with inanimate objects.

The engineered mice were significantly better than normal, though, at learning a water maze, in which they had to find and learn the location of an underwater platform. They were also better at relearning a new position of the platform after it was moved.

"When you manipulate a brain, you usually don't improve it," Dr. Südhof said. "The fact that we get an improvement is very good. It shows we're changing something specific; we're affecting how the brain processes information."

Other tests of coordination, anxiety and motor ability showed normal results, indicating that the changes in brain activity were specific, Dr. Südhof said.

The researchers also studied the patterns of electrical activity in the brain. Normally, some nerve cells halt, or inhibit, other nerve cells from firing, while others excite action in their neighbors. An imbalance in the normal pattern is thought to be involved in autism.

Nerve cells from the genetically engineered mice showed a significantly greater inhibitory action than their normal littermates, even though only about 10 percent of the normal amount of neuroligin-3 was present. This finding was a surprise, as other studies have indicated that a loss of inhibitory action might be involved in autism spectrum disorders, the researchers said.

The results indicate that focusing on inhibitory action might be a way to treat autistic behaviors, said Dr. Südhof, director of the Gill Center for Research on Brain Cell Communication and the C. Vincent Prothro Center for Research in Basic Neuroscience. He is a Howard Hughes Medical Institute investigator at UT Southwestern.
-end-
Other UT Southwestern researchers involved in the study were Dr. Katsuhiko Tabuchi, instructor of neuroscience; Dr. Jacqueline Blundell, postdoctoral researcher in neurology; Mark Etherton, medical student; Dr. Robert Hammer, professor of biochemistry and in the Cecil H. and Ida Green Center for Reproductive Biology Sciences; Dr. Xinran Liu, assistant professor of neuroscience and molecular genetics; and Dr. Craig Powell, assistant professor of neurology and psychiatry.

The work was supported by the National Institutes of Health, HHMI and Autism Speaks.

This news release is available on our World Wide Web home page at http://www.utsouthwestern.edu/home/news/index.html

To automatically receive news releases from UT Southwestern via e-mail, subscribe at www.utsouthwestern.edu/receivenews

Dr. Thomas Südhof -- http://www.utsouthwestern.edu/findfac/professional/0,2356,17079,00.html

UT Southwestern Medical Center

Related Autism Articles from Brightsurf:

Autism-cholesterol link
Study identifies genetic link between cholesterol alterations and autism.

National Autism Indicators Report: the connection between autism and financial hardship
A.J. Drexel Autism Institute released the 2020 National Autism Indicators Report highlighting the financial challenges facing households of children with autism spectrum disorder (ASD), including higher levels of poverty, material hardship and medical expenses.

Autism risk estimated at 3 to 5% for children whose parents have a sibling with autism
Roughly 3 to 5% of children with an aunt or uncle with autism spectrum disorder (ASD) can also be expected to have ASD, compared to about 1.5% of children in the general population, according to a study funded by the National Institutes of Health.

Adulthood with autism
The independence that comes with growing up can be scary for any teenager, but for young adults with autism spectrum disorder and their caregivers, the transition from adolescence to adulthood can seem particularly daunting.

Brain protein mutation from child with autism causes autism-like behavioral change in mice
A de novo gene mutation that encodes a brain protein in a child with autism has been placed into the brains of mice.

Autism and theory of mind
Theory of mind, or the ability to represent other people's minds as distinct from one's own, can be difficult for people with autism.

Potential biomarker for autism
A study of young children with autism spectrum disorder published in JNeurosci reveals altered brain waves compared to typically developing children during a motor control task.

Autism often associated with multiple new mutations
Most autism cases are in families with no previous history of the disorder.

State laws requiring autism coverage by private insurers led to increases in autism care
A new study led by researchers at the Johns Hopkins Bloomberg School of Public Health has found that the enactment of state laws mandating coverage of autism spectrum disorder (ASD) was followed by sizable increases in insurer-covered ASD care and associated spending.

Autism's gender patterns
Having one child with autism is a well-known risk factor for having another one with the same disorder, but whether and how a sibling's gender influences this risk has remained largely unknown.

Read More: Autism News and Autism Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.