Shank3 mutant mice display autistic-like behaviours and striatal dysfunction
By J. Peça, C. Feliciano, J. Ting, Wenting Wang, Michael F. Wells, T. Venkatraman, C. Lascola, Z. Fu, G. Feng. Nature, 2011
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Autism spectrum disorders (ASDs) comprise a range of disorders that share a core of neurobehavioural deficits characterized by widespread abnormalities in social interactions, deficits in communication as well as restricted interests and repetitive behaviours. The neurological basis and circuitry mechanisms underlying these abnormal behaviours are poorly understood. SHANK3 is a postsynaptic protein, whose disruption at the genetic level is thought to be responsible for the development of 22q13 deletion syndrome (Phelan–McDermid syndrome) and other non-syndromic ASDs. Here we show that mice with Shank3 gene deletions exhibit self-injurious repetitive grooming and deficits in social interaction. Cellular, electrophysiological and biochemical analyses uncovered defects at striatal synapses and cortico-striatal circuits in Shank3 mutant mice. Our findings demonstrate a critical role for SHANK3 in the normal development of neuronal connectivity and establish causality between a disruption in the Shank3 gene and the genesis of autistic-like behaviours in mice.
Subfields: Cognitive Neuroscience, Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/24d3a6c1398e18439fbee6b0bfa001273e981330
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Citations in the corpus
- Genome-wide prediction and functional characterization of the genetic basis of autism spectrum disorder (2016, background): “In addition, the striatum was identified here as a key locus of autism pathology throughout fetal development, a finding of particular relevance to repetitive behaviors as explored in mouse models that have both construct and face validity 36 .”
- Mechanisms underlying microbial-mediated changes in social behavior in mouse models of Autism Spectrum Disorder (2018, neutral): “Social deficits are one of the most salient features of individuals with ASD (American Psychiatric Association, 2013), and Shank3B / mice exhibit impaired social behavior (Peça et al., 2011).”
- Synaptic dysfunction in neurodevelopmental disorders associated with autism and intellectual disabilities. (2012, background): “…mutant mice have been characterized: one termed Shank3A in which the long isoform (Shank3 α ) is ablated by deletion of the ankyrin repeats, and a second termed Shank3B in which the PDZ domain is targeted, thus eliminating both the long α isoform and short Shank3 β isoform (Peça et al. 2011).”