UCLA geneticists have created a mouse model for autism that opens a window into the biological mechanisms that underlie the disease and offers a promising way to test new treatment approaches. The scientific paper, which was published in the September 30 edition of the journal Cell, reported that autistic mice behave similar to people on the autism spectrum; thus, suggesting that mice and human brains are wired surprisingly alike. The animals also responded well to the FDA-approved drug with risperidone , which is prescribed to autism patients to treat repetitive behaviors often associated with the disease. “Though many genes have been linked to autism, it remains unclear what goes awry to increase a person’s susceptibility to the disorder,” explained Dr. Daniel Geschwind, director of the Center for Autism Research and Treatment at the Semel Institute for Neuroscience and Human Behavior at UCLA.
The UCLA team focused on a gene called CNTNAP2 (contactin associated protein-like 2), which scientists believe plays an important role in brain circuits responsible for language and speech. Previous research has linked common CNTNAP2 variants to heightened autism risk in the general population, while rare variants can lead to an inherited form of autism called cortical dysplasia-focal epilepsy syndrome (CDFE). UCLA researchers studied mice lacking CNTNAP2 and found that the animals demonstrated many features of human autism, including abnormal vocal communication, irregular social interaction and repetitive behaviors. The animals were hyperactive and suffered epileptic seizures similar to those occurring in patients with CDFE.
A closer look at the animals’ brains before their seizures set in revealed abnormal development of brain-cell circuitry. The problems included irregularities in how neurons travel from their site of origin to their final position in the brain and in how groups of neurons communicate with each other. The animals also possessed fewer nerve cells that connect the neurons that carry impulses into the central nervous system with those that transmit impulses out to the rest of the body.
This finding dovetails with Geschwind’s earlier research, which found that children carrying the CNTNAP2 variant possess a disjointed brain. Their frontal lobe is over-connected to itself and poorly connected to the rest of the brain. Communication with the back of the brain was particularly diminished.
“Our findings suggest that evolution has maintained the repetitive behaviors related to autism across species,” Geschwind said. “If the same is true of social behaviors, we will use the mouse model to study potential therapies that may one day help people with autism.”
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