Most cases of autism are “sporadic,” meaning the cause of the disease is unknown. Scientists think that 10 to 20 genes may act together to increase risk for the disease. A few genetic mutations have been linked to rare cases of familial autism, which appears to be the case for PTEN. It’s not yet clear if PTEN is also involved in sporadic autism; however, the new findings add the gene to a list of potential suspects.
Parada adds that mutations in two other genes in the same pathway as PTEN have also been linked to rarer forms of autism, which hints that this pathway could be involved in the sporadic form of the disease.
Parada and team are now refining their analysis, knocking out the PTEN gene in specific subsets of cells to determine the particular brain area linked to social deficits. “One of the things we hope this will tell us is the anatomical location of autism,” says Parada. “The findings could only pertain to subset of people with autism, but it could be that a larger percentage than we think have problems in this pathway.”
In addition, the researchers are currently testing drugs that target the PTEN pathway, which is also involved in cancer, to see if they can reverse the social deficits in mice.
Scientists don’t know why knocking out the PTEN gene leads to these specific behavioral problems, but Parada speculates the deficits are linked to overloaded synaptic circuits. “A normal hippocampal cell has about 30,000 synapses, while a cell with PTEN knocked out has about 60,000 synapses, some in wrong place,” he says. “If you overload the circuit, you impair the current of neuronal information.”
Ultimately, the complexity of the human brain may make it impossible to create models that replicate all aspects of autism. “Many autistic people have problems with language,” says Anthony Wynshaw-Boris, a geneticist at the University of California, San Diego. “Mice don’t have language, so you can’t look at that.”