ArticleNature2012
Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 364 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
364 citing papers in PubMed, 2 syntheses or guidelines pooled it, 653 citations in OpenAlex.
- Pooled it
- Genetic variability in scaffolding proteins and risk for schizophrenia and autism-spectrum disorders: a systematic review.Journal of psychiatry & neuroscience : JPN · 2018Pooled it
- Evidence supporting the role of GIGYF2 in synapse development and autism.Molecular psychiatry · 2026Article
- Disruption of FOXG1 Impairs the Development of Striatal dSPNs, Thereby Contributing to ASD-Like Phenotypes.Neuroscience bulletin · 2026Article
- Social regression stems from a latent phase of GABAergic dysfunction and sensory breakdown in a model of synaptopathy.Molecular psychiatry · 2026Article
- Genetic mutations and synaptic dysfunctions in social interaction disorders: insights from invertebrate models to humans.Metabolic brain disease · 2026Review
- De novo variants in NPTN cause a neurodevelopmental disorder with autism and neuroplastin-PMCA hypofunction.Genome medicine · 2026Article
- Epigenetic and Transcriptomic Pathways Underlying Animal Models of Cognitive and Psychiatric Disorders: A Scoping Review.Current issues in molecular biology · 2026Review
- Sh3rf3 Deficiency drives autism-like behaviors via presynaptic dysfunction in mice.Molecular psychiatry · 2026Article
- Shank3 related oligodendrocyte alterations in autism are restored by Erk pathway inhibition.Molecular psychiatry · 2026Article
- Genetic Variants from Large Cohorts and Familial Studies Implicate Common Mechanisms in Schizophrenia.Biology · 2026Review
- How copy number variations shape brain developmental disorders: Unraveling the synaptic puzzle.Psychiatry and clinical neurosciences · 2026Review
- Kv4.2The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Article
- Occludin deficiency is associated with developmental impairment, locomotor dysfunction, and social deficiencies.Tissue barriers · 2026Article
- Hypersynchronous iPSC-derived SHANK2 neuronal networks are rescued by mGluR5 agonism.Stem cell reports · 2025Article
- Heightened empathic responses led by imbalanced cortico-amygdala circuit inbioRxiv : the preprint server for biology · 2025Article
- Demyelination-induced glutamatergic imbalance mediates hippocampal Hyperexcitability.Neurobiology of disease · 2025Article
- A Frank Assessment of SHANK: Impacts of Pathogenic Variations in SHANK3 on Preclinical Models of Phelan McDermid Syndrome.Autism research : official journal of the International Society for Autism Research · 2025Review
- Shank3 modulates Rpl3 expression and protein synthesis via mGlu5: implications for Phelan McDermid syndrome.Molecular psychiatry · 2025Article
304 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 9 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autism spectrum disorders comprise a range of neurodevelopmental disorders characterized by deficits in social interaction and communication, and by repetitive behaviour. Mutations in synaptic proteins such as neuroligins, neurexins, GKAPs/SAPAPs and ProSAPs/Shanks were identified in patients with autism spectrum disorder, but the causative mechanisms remain largely unknown. ProSAPs/Shanks build large homo- and heteromeric protein complexes at excitatory synapses and organize the complex protein machinery of the postsynaptic density in a laminar fashion. Here we demonstrate that genetic deletion of ProSAP1/Shank2 results in an early, brain-region-specific upregulation of ionotropic glutamate receptors at the synapse and increased levels of ProSAP2/Shank3. Moreover, ProSAP1/Shank2(-/-) mutants exhibit fewer dendritic spines and show reduced basal synaptic transmission, a reduced frequency of miniature excitatory postsynaptic currents and enhanced N-methyl-d-aspartate receptor-mediated excitatory currents at the physiological level. Mutants are extremely hyperactive and display profound autistic-like behavioural alterations including repetitive grooming as well as abnormalities in vocal and social behaviours. By comparing the data on ProSAP1/Shank2(-/-) mutants with ProSAP2/Shank3αβ(-/-) mice, we show that different abnormalities in synaptic glutamate receptor expression can cause alterations in social interactions and communication. Accordingly, we propose that appropriate therapies for autism spectrum disorders are to be carefully matched to the underlying synaptopathic phenotype.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.