ArticleNature2017
Autism gene Ube3a and seizures impair sociability by repressing VTA Cbln1.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
91 citing papers in PubMed, 2 syntheses or guidelines pooled it, 153 citations in OpenAlex.
- A Systematic Review of Brainstem Contributions to Autism Spectrum Disorder.Frontiers in integrative neuroscience · 2021Pooled it
- A multifaceted approach for analyzing complex phenotypic data in rodent models of autism.Molecular autism · 2019Pooled it
- GluDs are ionotropic dopamine receptors tuned by G-proteins.bioRxiv : the preprint server for biology · 2026Article
- Neonatal social communication and single genes predict the variability of post-pubertal social behavior in a mouse model of paternal 15q11-13 duplication.Research square · 2026Article
- Glutamate Delta 1 Receptor in Synapses, Circuits, and Disease.The European journal of neuroscience · 2026Review
- Atypical case of Rett syndrome with concurrentWorld journal of clinical pediatrics · 2025Article
- Double-hit of MIA and Nod2 deficiency induces sex-specific offspring behavioral abnormalities through placental dysregulation.Translational psychiatry · 2025Article
- Restoration of NEXMIF expression rescues abnormalities in gene transcription, neuron maturation and autistic-like behaviors in Nexmif knockout mice.Translational psychiatry · 2025Article
- Atypical Cadherin FAT2 Is Required for Synaptic Integrity and Motor Behaviors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Optimized isolation of enzymatically active ubiquitin E3 ligase E6AP/UBE3A from mammalian cells.Protein expression and purification · 2025Article
- Unraveling the Roles of UBE3A in Neurodevelopment and Neurodegeneration.International journal of molecular sciences · 2025Review
- Prenatal Exposure to Azadiradione Leads to Developmental Disabilities.Molecular neurobiology · 2025Article
- Role of androgen receptors in sexually dimorphic phenotypes in UBE3A-dependent autism spectrum disorder.iScience · 2025Article
- NEXMIF overexpression is associated with autism-like behaviors and alterations in dendritic arborization and spine formation in mice.Frontiers in neuroscience · 2025Article
- Glial expression of Drosophila UBE3A causes spontaneous seizures that can be modulated by 5-HT signaling.Neurobiology of disease · 2024Article
- Increased GluK1 Subunit Receptors in Corticostriatal Projection from the Anterior Cingulate Cortex Contributed to Seizure-Like Activities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Social and emotional alterations in mice lacking the short dystrophin-gene product, Dp71.Behavioral and brain functions : BBF · 2024Article
- Sex-biasing influence of autism-associatedScience advances · 2024Article
- Sexually dimorphic phenotypes and the role of androgen receptors in UBE3A-dependent autism spectrum disorder.bioRxiv : the preprint server for biology · 2024Article
- mRNA nuclear retention reduces AMPAR expression and promotes autistic behavior in UBE3A-overexpressing mice.EMBO reports · 2024Article
31 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
15 authors at 2 institutions in 1 country.
Funding
Abstract
Maternally inherited 15q11-13 chromosomal triplications cause a frequent and highly penetrant type of autism linked to increased gene dosages of UBE3A, which encodes a ubiquitin ligase with transcriptional co-regulatory functions. Here, using in vivo mouse genetics, we show that increasing UBE3A in the nucleus downregulates the glutamatergic synapse organizer Cbln1, which is needed for sociability in mice. Epileptic seizures also repress Cbln1 and are found to expose sociability impairments in mice with asymptomatic increases in UBE3A. This Ube3a-seizure synergy maps to glutamate neurons of the midbrain ventral tegmental area (VTA), where Cbln1 deletions impair sociability and weaken glutamatergic transmission. We provide preclinical evidence that viral-vector-based chemogenetic activation of, or restoration of Cbln1 in, VTA glutamatergic neurons reverses the sociability deficits induced by Ube3a and/or seizures. Our results suggest that gene and seizure interactions in VTA glutamatergic neurons impair sociability by downregulating Cbln1, a key node in the expanding protein interaction network of autism genes.
Indexed as
Identifiers
What OpenQuestion holds
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.