Mice with Shank3 Mutations Associated with ASD and Schizophrenia Display Both Shared and Distinct Defects

Yang Zhou, Tobias Kaiser, Patrícia Monteiro, Xiangyu Zhang, Marie S. Van der Goes, Dongqing Wang, Boaz Barak, Menglong Zeng, Chenchen Li, Congyi Lu, Michael Wells, Aldo Amaya, Shannon Nguyen, Michael Lewis, Neville Sanjana, Yongdi Zhou, Mingjie Zhang, Feng Zhang, Zhanyan Fu, Guoping Feng

Research output: Contribution to journalArticle

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 mutation 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.

Original languageEnglish (US)
Pages (from-to)147-162
Number of pages16
JournalNeuron
Volume89
Issue number1
DOIs
StatePublished - Jan 6 2016
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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    Zhou, Y., Kaiser, T., Monteiro, P., Zhang, X., Van der Goes, M. S., Wang, D., Barak, B., Zeng, M., Li, C., Lu, C., Wells, M., Amaya, A., Nguyen, S., Lewis, M., Sanjana, N., Zhou, Y., Zhang, M., Zhang, F., Fu, Z., & Feng, G. (2016). Mice with Shank3 Mutations Associated with ASD and Schizophrenia Display Both Shared and Distinct Defects. Neuron, 89(1), 147-162. https://doi.org/10.1016/j.neuron.2015.11.023