Cortical synaptosomal proteomics study in autistic-like mouse models with different genes knocked out

Synaptic dysfunction is thought to be an important factor in triggering autism spectrum disorder (ASD), many ASD-related genes have been found to be associated with it; however, the pathological mechanisms of how these genes affect synaptic function and trigger ASD have yet to be clearly established. Here, CNTN4, SAPAP3 and SHANK3 were selected as genes to be tested, we performed SWATH proteomics to investigate the proteomes of the cerebral cortex and cerebral cortical synaptosomes of the mice with genes knocked out, respectively. The results showed that the deletion of the genes induced autistic-like behavior in mice, and changes in the expression of numerous neuron-associated proteins, compared to the control group. The alternation of synaptic plasticity, glutamatergic synapse, GABAergic synapse and various signaling pathways were identified in the enrichment analysis. Common proteins in all three proteomics were dominated by postsynaptic-associated proteins, indicating that restricted synaptic signaling needed to be focused on, which was also verified by transmission electron microscope observations. In conclusion, our proteomics studies indicated CNTN4, SAPAP3 and SHANK3 have important effects on synaptic growth and development as well as synaptic plasticity.