AUTHOR=Song Tian-Jia , Lan Xing-Yu , Wei Meng-Ping , Zhai Fu-Jun , Boeckers Tobias M. , Wang Jia-Nan , Yuan Shuo , Jin Meng-Ying , Xie Yu-Fei , Dang Wan-Wen , Zhang Chen , Schön Michael , Song Pei-Wen , Qiu Mei-Hong , Song Ya-Yue , Han Song-Ping , Han Ji-Sheng , Zhang Rong TITLE=Altered Behaviors and Impaired Synaptic Function in a Novel Rat Model With a Complete Shank3 Deletion JOURNAL=Frontiers in Cellular Neuroscience VOLUME=13 YEAR=2019 URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2019.00111 DOI=10.3389/fncel.2019.00111 ISSN=1662-5102 ABSTRACT=

Mutations within the Shank3 gene, which encodes a key postsynaptic density (PSD) protein at glutamatergic synapses, contribute to the genetic etiology of defined autism spectrum disorders (ASDs), including Phelan-McDermid syndrome (PMS) and intellectual disabilities (ID). Although there are a series of genetic mouse models to study Shank3 gene in ASDs, there are few rat models with species-specific advantages. In this study, we established and characterized a novel rat model with a deletion spanning exons 11–21 of Shank3, leading to a complete loss of the major SHANK3 isoforms. Synaptic function and plasticity of Shank3-deficient rats were impaired detected by biochemical and electrophysiological analyses. Shank3-depleted rats showed impaired social memory but not impaired social interaction behaviors. In addition, impaired learning and memory, increased anxiety-like behavior, increased mechanical pain threshold and decreased thermal sensation were observed in Shank3-deficient rats. It is worth to note that Shank3-deficient rats had nearly normal levels of the endogenous social neurohormones oxytocin (OXT) and arginine-vasopressin (AVP). This new rat model will help to further investigate the etiology and assess potential therapeutic target and strategy for Shank3-related neurodevelopmental disorders.