Mice with Shank3 Mutations Associated with ASD and Schizophrenia Display Both Shared and Distinct Defects
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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 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.
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Direct genetic evidence links ASD and schizophrenia.
“alongside direct genetic evidence that links ASD and schizophrenia (Cantor and Geschwind, 2008;Ellis et al, 2016;Zhou et al, 2016).”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Zhou et al, 2016
Animal models with genetic modifications can help pinpoint pathways specific to autism when a gene also underlies conditions like schizophrenia or bipolar disorder, as with SHANK3.
“Genetically modified animal models also can be used to distinguish the disease-specific pathways that are affected in ASD when the same gene is known to cause other neuropsychiatric disorders such as schizophrenia and bipolar disease, as is the case for SHANK3”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [398]
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- Authors
- 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.
- Affiliations
- McGovern Institute for Brain Research (US)
- Broad Institute (US)
- Hong Kong University of Science and Technology (HK)
- Corresponding author
- Feng, Guoping
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 89
- Issue
- 1
- Pages
- 147-162
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4754122
- OpenAlex
- W2196375380
- Cited by
- 325
- References
- 73
- Citations by year
- 2026: 18 · 2025: 28 · 2024: 26 · 2023: 24 · 2022: 41 · 2021: 28 · 2020: 41 · 2019: 35 · 2018: 33 · 2017: 34 · 2016: 16 · 2015: 1
- FWCI
- 19.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- Simons Center for the Social Brain at MIT
- Stanley Center for Psychiatric Research at Broad Institute
- National Institute of Mental Health (5R01MH097104)
- Poitras Center for Affective Disorders Research at MIT
- Nancy Lurie Marks Family Foundation
- Simons Foundation Autism Research Initiative
- Shenzhen Overseas Innovation Team Project (KQTD20140630180249366)
- Stanley Center for Psychiatric Research at the Broad Institute
- Portuguese Foundation for Science and Technology (SFRH/BD/33894/2009)
- Autism Science Foundation
- Research Grant Council of Hong Kong (AoE/M09/12)
- Brain & Behavior Research Foundation
- Dr. Ernst und Anita Bauer-Stiftung
- Henry E. Singleton Fellowship
- NIMH (DP1-MH100706)
- NINDS (R01-NS 07312401)
- NSF Waterman Award
- Keck
- Damon Runyon
- Searle Scholars
- Klingenstein
- Vallee
- Merkin
- Simons Foundations
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- SHANK3, autism spectrum disorder, schizophrenia, mouse model, synaptic transmission, striatum, prefrontal cortex, social interaction, social dominance, mRNA stability
- MeSH terms
- Autism Spectrum Disorder, Aging, Animals, Behavior, Animal, Disease Models, Animal, Hippocampus, Mice, Transgenic, Microfilament Proteins, Mutation, Nerve Tissue Proteins, Synaptic Transmission, Neurons, Schizophrenia, Social Behavior
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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