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Scientists Engineer Mice That Have Autism

Scientists Engineer Mice That Have Autism

10/05/11

WEDNESDAY, Oct. 5 (HealthDay News) -- Scientists have genetically engineered mice whose symptoms closely mimic autism in humans.

Though this isn't the first "mouse model" for autism, the mice in this study come closer to mirroring all of the core symptoms of the developmental disorder in humans, said senior study author Matthew Anderson, an assistant professor of neurology and pathology and director of neuropathology at Beth Israel Deaconess Medical Center and Harvard Medical School in Boston. To create these mice, the researchers altered a gene previously believed to play a role in the development of autism.

Autism is characterized by problems with social interaction, verbal and nonverbal communication and restricted interests and behaviors.

The "autistic mice" showed similar traits. Unlike ordinary mice, the genetically engineered versions showed little interest in interacting with other mice. While regular mice vocalize when they're together -- especially in response to receiving something highly rewarding such as sugar -- the autistic mice stayed quiet. The autistic mice also excessively groomed themselves, suggesting a repetitive behavior, Anderson said.

The study is published in the Oct. 5 issue of Science Translational Medicine.

In the study, the mice were engineered to have abnormality in the Ube3a gene on a region of the chromosome called 15q11-13. That region had been previously implicated in autism, as well as in Angelman syndrome, which can lead to developmental delays, speech difficulties, seizures and walking or balance difficulties.

Specifically, the mice in the study were bred to have triple copies of the Ube3a gene.

Although the gene that researchers manipulated in the mice has been linked to only about 3 percent of autism cases, it's actually among the most common genetic causes of the condition, Anderson said.

Also, by strengthening the evidence that the particular gene abnormality is strongly linked to autism, researchers say the mice may one day be useful in testing new drugs that could counteract the effects of the gene abnormality.

"Now that we have a good surrogate, we can test medications to see if their communication and social interaction improves," he said.

By using mice as their test subjects, researchers were able to closely study the brain tissue of the mice to see what's going wrong. With the Ube3a duplication, researchers found that defects in a particular aspect of communications between neurons, called the excitatory synapses.

Mary Blue, a neuroscientist at Kennedy Krieger Institute in Baltimore, said the paper is "very comprehensive" and a good example of a model for autism in that "they are seeing changes in social behavior, changes in repetitive behavior and changes in 'ultrasonic' vocalizations."

But it's not the only mouse model for autism. Other scientists have created models by manipulating other genes, she said, including her own lab, which is working on a mouse model that mimics the serotonin deficits associated with autism.

And even the best mouse model can only take research so far, Blue added. It's widely accepted that a single gene isn't to blame for autism, but that a variety of genes and environmental influences play a role.

One thing researchers didn't find when they engineered their autistic mice were alterations in brain structure that have been associated with autism in humans, such as a temporary increase in brain volume seen in infants and toddlers who go on to receive an autism diagnosis.

"Autism is multi-factorial. There can be genetic factors, but there is also an environmental aspect of it, which is what makes it very hard to model," she said.

And not everyone is convinced that any mouse could truly mimic the social and language deficits seen in people with autism, she added. "Most clinicians working with autism are not that interested in animal models because you can't model human communication in mice," she said. "Mice can't talk."

More information

The U.S. National Institutes of Health has more on autism.

Copyright © 2011 HealthDay. All rights reserved.

Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.

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