Scripps scientists find connection between gene mutation, key symptoms of autism

April 28, 2014

Scientists have known that abnormal brain growth is associated with autism spectrum disorder. However, the relationship has not been well understood. Now, scientists from The Scripps Research Institute (TSRI) have shown that mutations in a specific gene that is disrupted in some individuals with autism results in too much growth throughout the brain, and in specific problems in social interactions, at least in mouse models that mimic this risk factor in humans. The study, which focuses on the gene phosphatase and tensin homolog (PTEN), was published online by Human Molecular Genetics.

The TSRI team set out to explore whether mutations in PTEN result in widespread or localized overgrowth within the brain, and whether changes in brain growth are associated with broad or selective deficits in tests of autism-relevant behaviors in genetically altered mice. The team tested mice for autism spectrum disorder-related behaviors including mood, anxiety, intellectual, and circadian rhythm and/or sleep abnormalities. They found that PTEN mutant mice showed altered social behavior but few other changes—a more subtle difference than would have been predicted given the broad expression and critical cellular function of the gene. The results raise the question of how mutations in PTEN, a general regulator of growth, can have relatively selective effects on behavior and cognitive development.

“What was striking is that these were basically normal animals in terms of behavior, but there were consistent deficits in tests of social interaction and recognition—which approximate a major symptom of autism,” says Damon Page, PhD, who led the study. “This suggests that when most parts of the brain are overgrown, the brain somehow adapts to it with minimal effects on behavior in general. However, brain circuits relevant to social behavior are more vulnerable or less able to tolerate this overgrowth. Read the study abstract.

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