Autistic mice act a lot like human patients

Sep 29, 2011

UCLA scientists 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.

Published in the Sept. 30 edition of Cell, the research found that autistic mice display remarkably similar symptoms and behavior as children and adults on the autism spectrum. The animals also responded well to an FDA-approved drug prescribed to autism patients to treat 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, who holds the Gordon and Virginia MacDonald Distinguished Chair in and is a professor of neurology at the David Geffen School of Medicine at UCLA and director of the Center for and Treatment at the Semel Institute for Neuroscience and Human Behavior at UCLA. "We developed a to observe how a gene variant commonly linked to human autism reveals itself in mice."

The UCLA team focused on a gene called CNTNAP2 (contactin associated protein-like 2), which scientists believe plays an important role in 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 , irregular social interaction and repetitive behaviors. The animals were hyperactive and suffered like 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 observations are consistent with theories suggesting that autism rewires the brain to reduce long-range connections and boost short-range connections," said Geschwind. "The front of the brain talks mostly with itself. It doesn't communicate as much with other parts of the brain and lacks long-range connections to the back of the brain."

Geschwind admits that he initially had low expectations of the mouse model and was surprised by its findings. He never expected the behaviors of autistic mice and autistic persons to so closely resemble each other.

"I did not expect to see the same behaviors in mice as in humans because we don't know how many neural pathways are shared between the two species," said Geschwind. "This suggests the pathways are very similar – surprisingly so."

The mice also responded well to treatment with risperidone, an antipsychotic drug that was the first to win FDA approval for treating symptoms of autism spectrum disorder.

Animals given the drug grew less hyperactive, showed less repetitive grooming behavior and were better at building nests. Consistent with previous observations in human patients, however, the mice did not show improvement in social interactions.

"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 ."

His lab next aims to develop drug treatments to improve social skills and use the mouse model to explore the different brain-cell pathways that influence core autistic behaviors.

Explore further: Researchers successfully clone adult human stem cells

Provided by University of California - Los Angeles

5 /5 (2 votes)
add to favorites email to friend print save as pdf

Related Stories

Study finds first-ever genetic animal model of autism

Dec 09, 2007

By introducing a gene mutation in mice, investigators have created what they believe to be the first accurate model of autism not associated with a broader neuropsychiatric syndrome, according to research presented at the ...

Gene mutation is linked to autism-like symptoms in mice

Feb 23, 2010

(PhysOrg.com) -- When a gene implicated in human autism is disabled in mice, the rodents show learning problems and obsessive, repetitive behaviors, researchers at UT Southwestern Medical Center have found.

Re-creating autism, in mice

Mar 21, 2011

(PhysOrg.com) -- By mutating a single gene, researchers at MIT and Duke have produced mice with two of the most common traits of autism — compulsive, repetitive behavior and avoidance of social interaction.

Recommended for you

Researchers successfully clone adult human stem cells

Apr 18, 2014

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

Researchers develop new model of cellular movement

Apr 18, 2014

(Phys.org) —Cell movement plays an important role in a host of biological functions from embryonic development to repairing wounded tissue. It also enables cancer cells to break free from their sites of ...

For resetting circadian rhythms, neural cooperation is key

Apr 17, 2014

Fruit flies are pretty predictable when it comes to scheduling their days, with peaks of activity at dawn and dusk and rest times in between. Now, researchers reporting in the Cell Press journal Cell Reports on April 17th h ...

User comments : 0

More news stories

Biologists help solve fungi mysteries

(Phys.org) —A new genetic analysis revealing the previously unknown biodiversity and distribution of thousands of fungi in North America might also reveal a previously underappreciated contributor to climate ...

Researchers successfully clone adult human stem cells

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.