Shank3-related autism reversed in mouse model

About 1% of individuals with autism have a mutation or deletion involving a gene called Shank3. In a new study, researchers found that restoring the function of this gene reversed several symptoms of autism in Shank3-deficient mice. 

The Shank3 protein, found in the synapses between neurons, is a scaffold protein that helps to organize other proteins necessary to coordinate a cell’s response to incoming signals. Shank3 is found primarily in the striatum, a brain region involved in motor activity, emotional aspects of behavior, and decision-making.

In the new study, Yuan Mei and colleagues genetically engineered mice so their Shank3 gene was turned off during embryonic development but could be turned on later in life by adding tamoxifen to the animals’ diet. Mice with the inactive gene exhibit compulsive behavior, motor abnormalities, and anxiety, and they avoid other mice. 

Reactivating the gene in young adult mice eliminated their repetitive behavior and social avoidance but did not reverse their anxiety or motor symptoms. When the researchers reactivated the gene earlier, the mice’s anxiety and motor coordination also improved. The researchers also found that the density of dendritic spines, which help to transmit synaptic signals, markedly increased in the striatum of treated mice.

“This suggests,” study coauthor Guoping Feng says, “that even in the adult brain we have profound plasticity to some degree. There is more and more evidence showing that some of the defects are indeed reversible, giving hope that we can develop treatment for autistic patients in the future.”

Citations

“Adult restoration of Shank3 expression rescues selective autistic-like phenotypes,” Yuan Mei, Patricia Monteiro, Yang Zhou, JinAh Kim, Xian Gao, Zhanyan Fu, and Guoping Feng, Nature, February 17, 2016 (epub prior to print publication). Address: Guoping Feng, Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142. 

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“Neuroscientists reverse autism symptoms,” Anne Trafton, MIT News, February 17, 2016.