Mice with Shank3 Mutations Associated with ASD and Schizophrenia Display Both Shared and Distinct Defects
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Author(s)
Amaya, Aldo
Nguyen, Shannon
Lewis, Michael
Zhou, Yongdi
Zhang, Mingjie
Zhou, Yang
Kaiser, Tobias
Monteiro, Patricia
Zhang, Xiangyu
Van der Goes, Marie-Sophie
Date Issued
December 2015
Journal
Neuron
Publisher
Elsevier/Cell Press
Citation
Zhou, Yang, et al. “Mice with Shank3 Mutations Associated with ASD and Schizophrenia Display Both Shared and Distinct Defects.” Neuron 89, 1 (January 2016): 147–162 © 2016 Elsevier Inc
Version
Author's final manuscript
Abstract
Genetic studies have revealed significant overlaps of risk genes among psychiatric disorders. However, it is not clear how different mutations of the same gene contribute to different disorders. We characterized two lines of mutant mice with Shank3 mutations linked to ASD and schizophrenia. We found both shared and distinct synaptic and behavioral phenotypes. Mice with the ASD-linked InsG3680 mutatio n manifest striatal synaptic transmission defects before weaning age and impaired juvenile social interaction, coinciding with the early onset of ASD symptoms. On the other hand, adult mice carrying the schizophrenia-linked R1117X mutation show profound synaptic defects in prefrontal cortex and social dominance behavior. Furthermore, we found differential Shank3 mRNA stability and SHANK1/2 upregulation in these two lines. These data demonstrate that different alleles of the same gene may have distinct phenotypes at molecular, synaptic, and circuit levels in mice, which may inform exploration of these relationships in human patients.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
McGovern Institute for Brain Research at MIT
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.NEURON.2015.11.023
