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Neuron DOI:10.1016/j.neuron.2015.11.023

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

Publication TypeJournal Article
Year of Publication2016
AuthorsZhou, Y, Kaiser, T, Monteiro, P, Zhang, X, Van der Goes, MS, 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
Date Published2016 Jan 06
KeywordsAging, Animals, Autism Spectrum Disorder, Behavior, Animal, Disease Models, Animal, Hippocampus, Mice, Transgenic, Mutation, Nerve Tissue Proteins, Neurons, Schizophrenia, Social Behavior, Synaptic Transmission

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.


Alternate JournalNeuron
PubMed ID26687841
PubMed Central IDPMC4754122
Grant ListR01 MH097104 / MH / NIMH NIH HHS / United States
R01 MH110049 / MH / NIMH NIH HHS / United States
5R01MH097104 / MH / NIMH NIH HHS / United States
DP1-MH100706 / DP / NCCDPHP CDC HHS / United States
DP1 MH100706 / MH / NIMH NIH HHS / United States
R01-NS 07312401 / NS / NINDS NIH HHS / United States