Evidence map›Paper›PMID 40066778›Full record

ArticleChinese medical journal2026

Modeling epilepsy by loss-of-function of the CUG-binding protein Elav-like family member 2 in zebrafish with multi-omics analysis.

Xiaoqian Wang, Jia Zhang, Xueyi Rao, Yanyan Liu, Ziyuan Lin, Feng Chen, Rong Luo, Huaqin Sun, Jing Gan

Abstract read
In one paragraph

Article in Chinese medical journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Xiaoqian WangDepartment of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Jia ZhangKey Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan 610041, China.
Xueyi RaoDepartment of Medical Genetics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Yanyan LiuDepartment of Medical Genetics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Ziyuan LinSichuan University - Chinese University of Hong Kong Joint Laboratory for Reproductive Medicine, Zebrafish Research Platform, Chengdu, Sichuan 610000, China.
Feng ChenSichuan University - Chinese University of Hong Kong Joint Laboratory for Reproductive Medicine, Zebrafish Research Platform, Chengdu, Sichuan 610000, China.
Rong LuoDepartment of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Huaqin SunSichuan University - Chinese University of Hong Kong Joint Laboratory for Reproductive Medicine, Zebrafish Research Platform, Chengdu, Sichuan 610000, China.
Jing GanDepartment of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe CUG-binding protein Elav-like family member 2 ( CELF2 ) gene has been linked to the pathogenesis of epilepsy, but its precise role remains unclear. This study aimed to investigate the pathogenic mechanisms of CELF2  mutation in epilepsy, utilizing zebrafish models to explore its molecular pathways and biological impact.

methodsWhole-exome sequencing was performed to identify CELF2  mutations associated with epilepsy. CELF2 zebrafish model was generated using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-related protein 9 technology and morpholinos, followed by behavioral and electroencephalographic analyses to confirm epileptic phenotypes. Proteomic and metabolomic analyses were conducted to examine the impact of CELF2  deficiency on metabolic pathways, and single-cell sequencing was used to assess alterations in neuronal cell populations.

resultsAn infant with infantile epileptic spasms syndrome associated with a CELF2 (p.Pro520Arg) gene mutation was reported. We established zebrafish models with celf2  gene knockout and knockdown and found that zebrafish with celf2  mutations exhibited epilepsy-like behaviors, which could be rescued by injection of CELF2 wild-type mRNA. Significant changes were observed in crucial marker genes associated with the nervous system in the celf2+/-  group, including FOS , BDNF , NPAS4 , GABRA1 , GABRG2 , and PYYA . Disruptions in lipid metabolism, heat shock protein 90 beta1 (Hsp90b1), were identified in proteomic and metabolomic analyses. Single-cell sequencing showed changes in nucleosome localization, nucleosome DNA binding, arginine and proline metabolic pathways, gonadotropin-releasing hormone signaling pathway, and nucleotide-binding oligomerization domain receptor signaling pathway.

conclusionsOur study has revealed a promising association between defects in the CELF2  gene and epilepsy using a zebrafish model, suggesting that CLEF2 is a causative gene in epilepsy. These findings not only indicate the potential impact on the biological process influenced by the CELF2  gene defect but also offer hopeful insights into the pathogenesis of epilepsy and potential therapeutic targets.

Indexed as

CELF ProteinsEpilepsyZebrafish ProteinsAnimalsDisease Models, AnimalHumansMultiomicsMutationProteomicsZebrafishCELF ProteinsZebrafish ProteinsEpilepsyMulti-omicsSingle-cell sequencingZebrafish model

Identifiers

PMID40066778
PMCPMC12875712

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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.