Elsevier

Behavioural Brain Research

Volume 251, 15 August 2013, Pages 65-74
Behavioural Brain Research

Research report
Autism-related behavioral abnormalities in synapsin knockout mice

https://doi.org/10.1016/j.bbr.2012.12.015Get rights and content
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Abstract

Several synaptic genes predisposing to autism-spectrum disorder (ASD) have been identified. Nonsense and missense mutations in the SYN1 gene encoding for Synapsin I have been identified in families segregating for idiopathic epilepsy and ASD and genetic mapping analyses have identified variations in the SYN2 gene as significantly contributing to epilepsy predisposition. Synapsins (Syn I/II/III) are a multigene family of synaptic vesicle-associated phosphoproteins playing multiple roles in synaptic development, transmission and plasticity. Lack of SynI and/or SynII triggers a strong epileptic phenotype in mice associated with mild cognitive impairments that are also present in the non-epileptic SynIII−/− mice. SynII−/− and SynIII−/− mice also display schizophrenia-like traits, suggesting that Syns could be involved in the regulation of social behavior. Here, we studied social interaction and novelty, social recognition and social dominance, social transmission of food preference and social memory in groups of male SynI−/−, SynII−/− and SynIII−/− mice before and after the appearance of the epileptic phenotype and compared their performances with control mice. We found that deletion of Syn isoforms widely impairs social behaviors and repetitive behaviors, resulting in ASD-related phenotypes. SynI or SynIII deletion altered social behavior, whereas SynII deletion extensively impaired various aspects of social behavior and memory, altered exploration of a novel environment and increased self-grooming. Social impairments of SynI−/− and SynII−/− mice were evident also before the onset of seizures. The results demonstrate an involvement of Syns in generation of the behavioral traits of ASD and identify Syn knockout mice as a useful experimental model of ASD and epilepsy.

Highlights

► Deletion of Syn isoforms widely impairs social behavior. ► SynII−/− mice display impaired social interaction, novelty and recognition. ► SynI−/− and SynII−/− mice are characterized by increased social dominance. ► Young and adult SynI−/− and SynIII−/− mice exhibit deficits in social transmission of food preference. ► Social deficits in SynI−/− and SynII−/− mice appear before the onset of epilepsy.

Keywords

Autism spectrum disorder
Social behavior
Synaptopathies
Synaptic vesicles
Epilepsy

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