A gene associated with autism that appears to be linked very specifically to the severity of social interaction deficits has been identified by Johns Hopkins scientists.
The gene, GRIP1 (glutamate receptor interacting protein 1), is a blueprint for a traffic-directing protein at synapses - those specialized contact points between brain cells across which chemical signals flow.
Identified more than a decade ago by Richard L. Huganir, professor and director of the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine, and a Howard Hughes Medical Institute investigator, GRIP1 regulates how fast receptors travel to a cell's surface, where they are activated by a brain-signaling chemical called glutamate, allowing neurons to communicate with one another.
The new study, which tracked two versions of GRIP1 in the genomes of 480 people with autism, and lends support to a prevailing theory that autism spectrum disorders (ASD), molecularly speaking, reflect an imbalance between inhibitory and excitatory signaling at synapses.
Using 10 mice genetically engineered to lack both normal and mutant GRIP proteins, researchers watched what happened when each animal was put into a box where it could choose between spending time with a mouse it hadn't encountered before, or an inanimate object. They compared the behaviors of these mice with 10 normal mice put into the same social situation. Mice lacking both GRIP1 and GRIP2 spent twice as much time as wild-type (normal) mice interacting with other mice as they did with inanimate objects.
"These results support a role for GRIP1 in social behavior and implicate its variants in modulating autistic behavior," Wang said.
Finally, the team looked at the behavioral analyses of individuals in two families, each with two autistic brothers, and correlated their scores on standard diagnostic tests that assessed social interaction with their genotypes for GRIP1 variants.
In one family, the brother with two copies of the GRIP1 mutant variety scored lower on social interaction tests than his brother who had only one copy of the GRIP1 variant. The boys' mother, although not diagnosed as autistic, had a history of restricted interests, poor eye contact and repetitive behavior. Tests showed she also carried one copy of the variant.
In a second family, the autistic brother with one copy of the GRIP1 variant had lower social interaction scores than his autistic sibling without a GRIP1 variant.
Because the GRIP1 gene resides in synapses where other genes also implicated in autism have been found, this location is potentially important in terms of clinical relevance, said Huganir.
The study was published in the Proceedings of the National Academy of Sciences.