Altered Behaviors and Impaired Synaptic Function in a Novel Rat Model With a Complete Shank3 Deletion

Mutations within the 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 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 , leading to a complete loss of the major SHANK3 isoforms. Synaptic function and plasticity of -deficient rats were impaired detected by biochemical and electrophysiological analyses. -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 -deficient rats. It is worth to note that -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 -related neurodevelopmental disorders.