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Differentially altered social dominance- and cooperative-like behaviors in Shank2- and Shank3-mutant mice

Differentially altered social dominance- and cooperative-like behaviors in Shank2- and Shank3-mutant mice
Han, Kyung AhYoon, Taek HanShin, JungsuUm, Ji WonKo, Jaewon
DGIST Authors
Um, Ji WonKo, Jaewon
Issue Date
Molecular Autism, 11(1), 87
Article Type
Author Keywords
AutismShank2Shank3Social cooperationSocial dominanceTube test
Background: Recent progress in genomics has contributed to the identification of a large number of autism spectrum disorder (ASD) risk genes, many of which encode synaptic proteins. Our understanding of ASDs has advanced rapidly, partly owing to the development of numerous animal models. Extensive characterizations using a variety of behavioral batteries that analyze social behaviors have shown that a subset of engineered mice that model mutations in genes encoding Shanks, a family of excitatory postsynaptic scaffolding proteins, exhibit autism-like behaviors. Although these behavioral assays have been useful in identifying deficits in simple social behaviors, alterations in complex social behaviors remain largely untested. Methods: Two syndromic ASD mouse models—Shank2 constitutive knockout [KO] mice and Shank3 constitutive KO mice—were examined for alterations in social dominance and social cooperative behaviors using tube tests and automated cooperation tests. Upon naïve and salient behavioral experience, expression levels of c-Fos were analyzed as a proxy for neural activity across diverse brain areas, including the medial prefrontal cortex (mPFC) and a number of subcortical structures. Findings: As previously reported, Shank2 KO mice showed deficits in sociability, with intact social recognition memory, whereas Shank3 KO mice displayed no overt phenotypes. Strikingly, the two Shank KO mouse models exhibited diametrically opposed alterations in social dominance and cooperative behaviors. After a specific social behavioral experience, Shank mutant mice exhibited distinct changes in number of c-Fos+ neurons in the number of cortical and subcortical brain regions. Conclusions: Our results underscore the heterogeneity of social behavioral alterations in different ASD mouse models and highlight the utility of testing complex social behaviors in validating neurodevelopmental and neuropsychiatric disorder models. In addition, neural activities at distinct brain regions are likely collectively involved in eliciting complex social behaviors, which are differentially altered in ASD mouse models. © 2020, The Author(s).
BioMed Central Ltd
Related Researcher
  • Author Ko, Jaewon Laboratory of Synapse Formation and Function
  • Research Interests Synapse Formation and Function; Neural Circuits; 뇌질환; animal model
Department of Brain and Cognitive SciencesSynapse Disorder Laboratory1. Journal Articles
Department of Brain and Cognitive SciencesLaboratory of Synapse Formation and Function1. Journal Articles

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