Mice with Shank3 Mutations Associated with ASD and Schizophrenia Display Both Shared and Distinct Defects
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; Wang, Dongqing; Barak, Boaz; Zeng, Menglong; Li, Chenchen; Lu, Congyi; Wells, Michael; Sanjana, Neville E; Zhang, Feng; Fu, Zhanyan; Feng, Guoping; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences; McGovern Institute for Brain Research at MIT
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
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