ArticleJCI insight2021
Scn2a severe hypomorphic mutation decreases excitatory synaptic input and causes autism-associated behaviors.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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
20 citing papers in PubMed, 31 citations in OpenAlex.
- Voltage-Gated Sodium Channel NaBiochemical genetics · 2026Article
- Characterization of Electrophysiological and Transcriptomic Alterations in Patient-Derived Neurons from CHAMP1 Syndrome.bioRxiv : the preprint server for biology · 2026Article
- Voltage-gated sodium channels in the nervous system: Molecular physiology to therapeutic interventions.Neural regeneration research · 2026Article
- Excitatory Dysfunction and Phenotypic Rescue in a Human Neuronal Model ofbioRxiv : the preprint server for biology · 2026Article
- Review
- Sex-Specific Behavioral Features of Juvenile and Adult Haploinsufficient Scn2aGenes, brain, and behavior · 2025Article
- The DEC2-SCN2A Axis is Essential for the Anticonvulsant Effects of Cannabidiol by Modulating Neuronal Plasticity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Restoration of excitation/inhibition balance enhances neuronal signal-to-noise ratio and rescues social deficits in autism-associatedbioRxiv : the preprint server for biology · 2025Article
- Voltage-gated sodium channels in genetic epilepsy: up and down of excitability.Journal of neurochemistry · 2024Review
- DecipheringArXiv · 2024Article
- Gene therapy as an emerging treatment forFundamental research · 2024Review
- Crosstalk among WEE1 Kinase, AKT, and GSK3 in Nav1.2 Channelosome Regulation.International journal of molecular sciences · 2024Article
- A neural perspective on the treatment of hypertension: the neurological network excitation and inhibition (E/I) imbalance in hypertension.Frontiers in cardiovascular medicine · 2024Review
- Exploring the mechanism of agarwood moxa smoke in treating sleep disorders based on GC-MS and network pharmacology.Frontiers in medicine · 2024Article
- Scn2a insufficiency alters spontaneous neuronal CaiScience · 2023Article
- Pathogenic SCN2A variants cause early-stage dysfunction in patient-derived neurons.Human molecular genetics · 2023Article
- Disruption of the autism-associated geneFrontiers in cellular neuroscience · 2023Article
- Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum.Physiological reviews · 2023Review
- Cellular and behavioral effects of altered NaV1.2 sodium channel ion permeability in Scn2aK1422E mice.Human molecular genetics · 2022Article
- Ionic Channels as Potential Targets for the Treatment of Autism Spectrum Disorder: A Review.Current neuropharmacology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
SCN2A, encoding the neuronal voltage-gated Na+ channel NaV1.2, is one of the most commonly affected loci linked to autism spectrum disorders (ASDs). Most ASD-associated mutations in SCN2A are loss-of-function mutations, but studies examining how such mutations affect neuronal function and whether Scn2a mutant mice display ASD endophenotypes have been inconsistent. We generated a protein truncation variant Scn2a mouse model (Scn2aΔ1898/+) by CRISPR that eliminates the NaV1.2 channel's distal intracellular C-terminal domain, and we analyzed the molecular and cellular consequences of this variant in a heterologous expression system, in neuronal culture, in brain slices, and in vivo. We also analyzed multiple behaviors in WT and Scn2aΔ1898/+ mice and correlated behaviors with clinical data obtained in human subjects with SCN2A variants. Expression of the NaV1.2 mutant in a heterologous expression system revealed decreased NaV1.2 channel function, and cultured pyramidal neurons isolated from Scn2aΔ1898/+ forebrain showed correspondingly reduced voltage-gated Na+ channel currents without compensation from other CNS voltage-gated Na+ channels. Na+ currents in inhibitory neurons were unaffected. Consistent with loss of voltage-gated Na+ channel currents, Scn2aΔ1898/+ pyramidal neurons displayed reduced excitability in forebrain neuronal culture and reduced excitatory synaptic input onto the pyramidal neurons in brain slices. Scn2aΔ1898/+ mice displayed several behavioral abnormalities, including abnormal social interactions that reflect behavior observed in humans with ASD and with harboring loss-of-function SCN2A variants. This model and its cellular electrophysiological characterizations provide a framework for tracing how a SCN2A loss-of-function variant leads to cellular defects that result in ASD-associated behaviors.
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.