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Gene linked to severity of autism's social dysfunction
Date:4/6/2011

h inhibitory and excitatory synapses, according to Wang.

Initially, looking under a microscope at normal mouse neurons and neurons with a mutant version of GRIP1, the investigators marked the receptor proteins with green fluorescence, added a chemical that promotes their "disappearance" deep inside a cell and timed the rates at which they disappeared leaving a cell unable to respond to signals from other cells. They also timed the reemergence of the protein back to the cell surface. With the GRIP1 mutant neurons, the receptors recycled to the surface twice as fast as in the normal neurons.

"If the receptors are recycling faster, the number of receptors on the surface is greater, so the cells are more sensitive to glutamate," Huganir explains. "The quicker the recycling, the more receptors on the surface and the stronger the excitatory transmission."

Even if just the excitatory synapses are affected, and the inhibitory ones don't change, that alone affects the relative balance of signaling, Huganir says.

Next, 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 says.

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, th
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Contact: Maryalice Yakutchik
myakutc1@jhmi.edu
443-287-2251
Johns Hopkins Medical Institutions
Source:Eurekalert

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