Lara J Duffney, Ping Zhong, Jing Wei, Emmanuel Matas, Jia Cheng, Luye Qin, Kaijie Ma, David M Dietz, Yuji Kajiwara, Joseph D Buxbaum, Zhen Yan
Haploinsufficiency of the Shank3 gene, which encodes a scaffolding protein at glutamatergic synapses, is a highly prevalent and penetrant risk factor for autism. Using combined behavioral, electrophysiological, biochemical, imaging, and molecular approaches, we find that Shank3-deficient mice exhibit autism-like social deficits and repetitive behaviors, as well as the significantly diminished NMDA receptor (NMDAR) synaptic function and synaptic distribution in prefrontal cortex. Concomitantly, Shank3-deficient mice have a marked loss of cortical actin filaments, which is associated with the reduced Rac1/PAK activity and increased activity of cofilin, the major actin depolymerizing factor...
June 9, 2015: Cell Reports