Using engineered mice, researchers at the University of Texas Southwestern Medical Center took an important step toward understanding the genetic basis of autism-spectrum disorders. Their work, published in the May 4th issue of Neuron, may lead to genetic treatments for a particular type of autism.
"We feel a certain degree of excitement and hope that, at the very least, this mouse model will represent a very useful model for studying the biology, the pathology and potential therapeutic treatments of, at the very least, that small number of patients with autism spectrum disorder," said Luis Parada, senior author on the study and director of the Southwestern Medical Center for Developmental Biology.
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The study focused on the pivotal gene PTEN (pronounced pee-ten). Certain mutations of PTEN can cause cancers such as tuberosclerosis and neurofibromatosis—conditions that, researchers discovered recently, are linked to autism.
Parada and his team set out to find a connection between the PTEN mutation and autistic-spectrum disorder by creating mice that carried the mutation. As these mice grew, Parada and his team subjected them to a barrage of cognitive tests. This work revealed remarkable differences between the mutants and their normal peers.
"The [mutant mice] were alive, they fed, they thrived, they didn't seem to have any sort of particular illnesses," Parada said. "However, when we looked at the mice a little more carefully, we could distinguish the mutant mice [from the others]."
The mice with altered PTEN were resistant to handling, just as autistic children can be resistant to hugging and touch. While the normal mice were more likely to respond to an unknown mouse than an unknown object, the mutant mice found the object preferable. When introduced to an unknown mouse as well as a familiar mouse, the normal mice pursued friendship with the familiar mouse first, while the mutant mice ignored both.
The diagnosis was clear: The engineered mutation had created mice with autistic-spectrum disorders. Parada's discovery does not mean that the Pten gene is responsible for all autistic-spectrum disorders, but it indicates that it has an effect on versions carrying a high co-morbidity rate with cancers like tuberosclerosis and neurofibromatosis.
Parada's work represents an important step, said Anthony Wynshaw-Boris, a researcher in the cancer genetics program at University of California, San Diego, who has done similar work with mice.
"One hopes that, like other diseases, insights into the rare forms of autism will provide insight into more common forms," he said.