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 idiopathic epilepsy and ASD and genetic mapping analysis 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-/- 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 communication 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 wild-type littermates. We found that deletion of Syn isoforms widely impairs social behavior, social communication and repetitive behaviors, resulting in ASD-related phenotypes. SynI or SynIII deletion altered social behavior and communication, whereas SynII deletion extensively impaired various aspects of social behavior and memory, altered environmental interest 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.

Autism-related behavioral abnormalities in synapsin knockout mice

VALTORTA , FLAVIA;
2013-01-01

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 idiopathic epilepsy and ASD and genetic mapping analysis 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-/- 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 communication 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 wild-type littermates. We found that deletion of Syn isoforms widely impairs social behavior, social communication and repetitive behaviors, resulting in ASD-related phenotypes. SynI or SynIII deletion altered social behavior and communication, whereas SynII deletion extensively impaired various aspects of social behavior and memory, altered environmental interest 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.
2013
autism; epilepsy; synapse
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/17600
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