Researchers have created mice with some vocal communication and social behavior problems that parallel those seen in autistic patients. The findings pave the way toward understanding exactly how genes cause some of the symptoms of autism, and appear in the 5 October issue of Science Translational Medicine.
“The study shows that something considered uniquely human—speech and communication characteristically defective in autism—can be measured in juvenile and adult mice and impaired by autism-related genes,” said Matthew P. Anderson, lead author of the study and professor of pathology and neurology at Harvard Medical School.
A reliable mouse model is also necessary for future testing of drugs that might treat autism in children and adults. Currently, it’s nearly impossible for autism researchers to confirm whether or not a particular gene is causative. Each patient potentially has hundreds of damaging mutations and finding enough people with the same mutation to make a strong statistical link is always an obstacle.
Matthew Anderson of Harvard Medical School discusses the research on the autism-mimicking mouse.[Video courtesy of Beth Israel Deaconess Medical Center; © Science/AAAS]
To get around these issues, scientists rely on the mouse model. But creating mice with the specific behavioral problems seen in autistic patients has been equally challenging.
In their experiment, Anderson and colleagues honed in on a gene called Ube3a. This gene is located on a particular region of the human chromosome called 15q11-13 that previous studies have linked to autism.
Ube3a itself has also been implicated in Angelman Syndrome, a developmental disorder that shares some symptoms with autism. Doubling and tripling the doses of the Ube3a gene in mice causes three core autism-related behaviors in the animals compared with normal mice: Reduced social interaction, impaired communication, and excessive repetitive behavior.
The researchers think that certain defects in how neurons communicate are responsible for the animals’ behavioral changes. Notably, the team did not notice any obvious changes in brain structure in the mice.
“This is a step forward in confirming that a common genetic change found in human autism actually causes the behavioral problems and helps focus our investigations into a specific biological pathway,” Anderson said.
There are scores of identified and yet-to-be identified autism-associated genes that individually or together cause autism. Mimicking of some of these symptoms in mice by boosting the gene dosage of Ube3a reveals a key piece of the puzzle, but there are many pieces left to find and fit together.
Read the abstract, “Increased Gene Dosage of Ube3a Results in Autism Traits and Decreased Glutamate Synaptic Transmission in Mice,” by Matthew P. Anderson and colleagues.