Mouse models of autism developed

Scientists at the University of California, Los Angeles (UCLA) have engineered a mouse model for autism that has pointed to a new understanding of the disorder and possible ways to evaluate new treatments.

The researchers developed a model to test how a gene variant, specifically the lack of an autism linked protein known as contactin associated protein-like 2 (CNTNAP2), expresses itself in the mice.

The CNTNAP2 gene is an important factor in brain circuits for control of language and speech. Prior experimentation shows that CNTNAP2 in its common variants can increase the risk for autism in the general population, while rarer variants are responsible for a form of inherited autism called cortical dysplasia-focal epilepsy syndrome (CDFE).

The mice that lacked CNTNAP2 were found to display many characteristics of human autism such as abnormal social interactions, repetitive behaviors, hyperactivity and epileptic seizures similar to those of patients with CDFE.

The fact that the absence of this gene causes behaviors stereotypic of autism suggests that CNTNAP2 is biologically instrumental in certain brain connections that autistic patients lack.

Furthering this hypothesis, the researchers found that immediately prior to the observed seizures, the mice did not exhibit normal development of brain-cell circuitry. Neurons travelled and communicated irregularly within the brain, supporting previous theories that autism causes short-range brain connections to be enhanced and long-range connections to be reduced.

Under this hypothesis, the disconnection of the front of the brain from the back causes an interruption in communication which can cause some autism-specific behaviors such as decreased social interaction and increased repetitive behaviors.

Autism at large is a neurobiological disorder that has been called a "national public health crisis" by the Centers for Disease Control and Prevention. Its spectrum disorders occur in one out of every 110 children in the United States. There is currently no cure for autism; though certain genes have been linked to autism, scientists are unsure what exactly triggers someone's heightened susceptibility.

One major implication of these findings is that future drug treatments for autism could be tested and developed using this engineered mouse model. Testing with the FDA-approved antipsychotic drug risperidone has yielded positive results in mice as well as humans — hyperactivity and repetitive activities were decreased. However, social interaction behaviors were unaffected by risperidone.

The scientists plan to use their current findings and the mouse model to try to develop new drug treatments and therapies targeted at improving social behaviors.

Researchers at the Hopkins School of Medicine conducted similar research released in June with a mouse model of autism that studied a gene called Shank3. Mutations in this gene cause autism-like behaviors because the communications between neurons at the synapses were affected. This study may similarly lend itself to the testing of drugs that could pinpoint and improve the social behaviors of patients living with autism.