ArticleThe Journal of physiology2013
Aberrant sodium channel activity in the complex seizure disorder of Celf4 mutant mice.
Article in The Journal of physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions.Nature neuroscience · 2021Pooled it
- Pathological disruption of CELF2 shuttling causes neuronal hyperactivity, learning deficits, and seizures.The Journal of clinical investigation · 2026Article
- CELF family of RNA-binding proteins: roles in disease biology and potential for therapeutic intervention.Cell communication and signaling : CCS · 2026Review
- Celf4 Regulates Excitability of Bushy Cells in the Cochlear Nucleus of the Mouse Brainstem.Cellular and molecular neurobiology · 2026Article
- The RNA-binding protein CELF4: from molecular regulatory networks to clinical translation in cross-system diseases.Frontiers in molecular biosciences · 2026Review
- Heterozygous CELF4 variants in the N-term region crucial for the RNA-binding activity lead to neurodevelopmental disorder and obesity.European journal of human genetics : EJHG · 2025Article
- Voltage-Gated Ion Channel Compensatory Effect in DEE: Implications for Future Therapies.Cells · 2024Review
- Vocal learning-associated convergent evolution in mammalian proteins and regulatory elements.Science (New York, N.Y.) · 2024Article
- Altered CELF4 splicing factor enhances pancreatic neuroendocrine tumors aggressiveness influencing mTOR and everolimus response.Molecular therapy. Nucleic acids · 2024Article
- Members of the CUGBP Elav-like family of RNA-binding proteins are expressed in distinct populations of primary sensory neurons.The Journal of comparative neurology · 2023Article
- Analysis of intraoperative human brain tissue transcriptome reveals putative risk genes and altered molecular pathways in glioma-related seizures.Epilepsy research · 2021Article
- Overlaps, gaps, and complexities of mouse models of Developmental and Epileptic Encephalopathy.Neurobiology of disease · 2021Review
- Voltage Gated Sodium Channel Genes in Epilepsy: Mutations, Functional Studies, and Treatment Dimensions.Frontiers in neurology · 2021Review
- Distinct functional alterations in SCN8A epilepsy mutant channels.The Journal of physiology · 2020Article
- Epilepsy-Related Voltage-Gated Sodium Channelopathies: A Review.Frontiers in pharmacology · 2020Review
- Linkage Evidence for a Two-Locus Inheritance of LQT-Associated Seizures in a Multigenerational LQT Family With a NovelFrontiers in neurology · 2019Article
- De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy.Journal of medical genetics · 2015Article
- Regulation of membrane excitability: a convergence on voltage-gated sodium conductance.Molecular neurobiology · 2015Review
- Convulsive seizures and SUDEP in a mouse model of SCN8A epileptic encephalopathy.Human molecular genetics · 2015Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Mice deficient for CELF4, a neuronal RNA-binding protein, have a complex seizure disorder that includes both convulsive and non-convulsive seizures, and is dependent upon Celf4 gene dosage and mouse strain background. It was previously shown that Celf4 is expressed predominantly in excitatory neurons, and that deficiency results in abnormal excitatory synaptic neurotransmission. To examine the physiological and molecular basis of this, we studied Celf4-deficient neurons in brain slices. Assessment of intrinsic properties of layer V cortical pyramidal neurons showed that neurons from mutant heterozygotes and homozygotes have a lower action potential (AP) initiation threshold and a larger AP gain when compared with wild-type neurons. Celf4 mutant neurons also demonstrate an increase in persistent sodium current (I(NaP)) and a hyperpolarizing shift in the voltage dependence of activation. As part of a related study, we find that CELF4 directly binds Scn8a mRNA, encoding sodium channel Na(v)1.6, the primary instigator of AP at the axon initial segment (AIS) and the main carrier of I(NaP). In the present study we find that CELF4 deficiency results in a dramatic elevation in the expression of Na(v)1.6 protein at the AIS in both null and heterozygous neurons. Together these results suggest that activation of Na(v)1.6 plays a crucial role in seizure generation in this complex model of neurological disease.
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