title: Autism-related behavioral abnormalities in synapsin knockout mice.
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.
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Greco
authors.forename: Francesca
authors.initials: F
authors.lastname: Managò
authors.forename: Valter
authors.initials: V
authors.lastname: Tucci
authors.forename: Hung-Teh
authors.initials: HT
authors.lastname: Kao
authors.forename: Flavia
authors.initials: F
authors.lastname: Valtorta
authors.forename: Fabio
authors.initials: F
authors.lastname: Benfenati
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000235:genetics*; D001522:Behavior, Animal / Q000502:physiology*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D006120:Grooming / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D021641:Recognition, Psychology / Q000502:physiology; D012919:Social Behavior; D012930:Social Dominance; D016704:Synapsins / Q000235:genetics*
chemical_list: D016704:Synapsins
keywords: Autism spectrum disorder; Epilepsy; Social behavior; Synaptic vesicles; Synaptopathies