Cell-Type-Specific Shank2 Deletion in Mice Leads to Differential Synaptic and Behavioral Phenotypes

Abstract

Shank2 is an excitatory postsynaptic scaffolding protein implicated in synaptic regulation and psychiatric disorders including autism spectrum disorders. Conventional Shank2-mutant (Shank2(-/-)) mice display several autistic-like behaviors, including social deficits, repetitive behaviors, hyperactivity, and anxiety-like behaviors. However, cell-type-specific contributions to these behaviors have remained largely unclear. Here, we deleted Shank2 in specific cell types and found that male mice lacking Shank2 in excitatory neurons (CaMKII-Cre;Shank2(fl/fl)) show social interaction deficits and mild social communication deficits, hyperactivity, and anxiety-like behaviors. In particular, male mice lacking Shank2 in GABAergic inhibitory neurons (Viaat-Cre;Shank2(fl/fl)) display social communication deficits, repetitive self-grooming, and mild hyperactivity. These behavioral changes were associated with distinct changes in hippocampal and striatal synaptic transmission in the two mouse lines. These results indicate that cell-type-specific deletions of Shank2 in mice lead to differential synaptic and behavioral abnormalities.