A new mouse model of autism created by scientists at the University of California-Los Angeles promises to mimic the disease more closely than previous animal models, according to a paper out today in the journal Cell. The mice possess the same mutation in the gene contactin associated protein-like 2 (CNTNAP2) seen in a small subset of people with autism. When individuals have two non-functioning versions of the gene, as found in two Amish families, they suffer a suite of symptoms such as epileptic seizures, language regression, hyperactivity and autism. The mice created by the UCLA team exhibit all of these symptoms, including the deficits in vocal communication and repetitive behaviors characteristic of autism linked to CNTNAP2 mutations.
The authors are cautiously optimistic about the new model. “One has to have a caveat that it’s hard to make a direct comparison between human and mouse behavior,” says Daniel Geschwind, the neuropsychiatrist at UCLA who led the investigation.
The model has impressed other scientists for marrying the genetic and behavioral aspects of autism seen in humans, and for its predictive validity. When given the drug Risperdal (risperidone), used to treat repetitive behaviors in humans with autism, the mice responded similarly, suggesting that the animals might be used to test novel treatments.
“That’s what really sets this model apart,” says Craig Powell, a neurologist who studies autism mouse models at the University of Texas Southwestern in Dallas. “They were able to use one of the two FDA-approved drugs for autism in humans and successfully cure a subset of behaviors in the model.” There are no other known autism mouse models, according to Powell, that satisfy all these criteria.
“It gives us more confidence that animal models can be used to test novel therapeutic compounds for autism,” says Powell.
Neuroscientist Guoping Feng from the Massachusetts Institute of Technology in Cambridge agrees that the model was “elegant.” He adds that the model suggests a previously unknown mechanism behind the disease — it showed that the mutated gene, CNTNAP2, affects the development of specific neurons in the mouse brain that primarily secrete the neurotransmitter GABA. In humans, this population of neurons is influenced by other autism-related genes. For this reason, Feng says this new model could inform treatments for individuals with autism beyond the subset with the CNTNAP2 mutation.
Image: Rama via Wikimedia Commons
