ArticlePloS one2017
Characterization of the first knock-out aldh7a1 zebrafish model for pyridoxine-dependent epilepsy using CRISPR-Cas9 technology.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Astrocyte redox imbalance underlies prelimbic neuronal hypoactivity and maladaptive affective behaviors in epilepsy.Science advances · 2026Article
- Employing zebrafish to understand genetic drivers of epilepsy-related comorbid behaviors.Frontiers in pharmacology · 2026Article
- Enhancing sudden unexpected death in epilepsy (SUDEP) research through development of common data elements.Epilepsia open · 2025Article
- Validating the antiseizure effects of vitexin and related flavone glycosides in zebrafish.Frontiers in pharmacology · 2025Article
- Zebrafish as an Innovative Tool for Epilepsy Modeling: State of the Art and Potential Future Directions.International journal of molecular sciences · 2023Review
- Pyridoxine-dependent epilepsy: Current perspectives and questions for future research.Annals of the Child Neurology Society · 2023Article
- Metabolomics analysis of antiquitin deficiency in cultured human cells and plasma: Relevance to pyridoxine-dependent epilepsy.Journal of inherited metabolic disease · 2023Article
- An Overview of Zebrafish Modeling Methods in Drug Discovery and Development.Advances in experimental medicine and biology · 2022Article
- Mutants of the Zebrafish KInternational journal of molecular sciences · 2021Article
- Phenotypic analysis of catastrophic childhood epilepsy genes.Communications biology · 2021Article
- Article
- Gene editing in plants: assessing the variables through a simplified case study.Plant molecular biology · 2020Article
- Phenotypic Characterization of Larval Zebrafish (Danio rerio) with Partial Knockdown of the cacna1a Gene.Molecular neurobiology · 2020Article
- Modeling Neuronal Diseases in Zebrafish in the Era of CRISPR.Current neuropharmacology · 2020Review
- Bi-allelic GOT2 Mutations Cause a Treatable Malate-Aspartate Shuttle-Related Encephalopathy.American journal of human genetics · 2019Article
- Intellectual Disability Associated With Pyridoxine-Responsive Epilepsies: The Need to Protect Cognitive Development.Frontiers in psychiatry · 2019Review
- High-throughput DNA Extraction and Genotyping of 3dpf Zebrafish Larvae by Fin Clipping.Journal of visualized experiments : JoVE · 2018Article
- Combining Zebrafish and CRISPR/Cas9: Toward a More Efficient Drug Discovery Pipeline.Frontiers in pharmacology · 2018Review
- Pyridoxine-dependent and other pyridoxine-responsive epilepsies-insights into phenotype overlapping and the long-term outcome in a cohort of 21 children.Frontiers in neurologyArticle
- A novel therapy for pyridoxine-dependent epilepsy due to biallelic pathogenic variants inTherapeutic advances in rare diseaseArticle
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pyridoxine dependent epilepsy (PDE) is caused by likely pathogenic variants in ALDH7A1 (PDE-ALDH7A1) and inherited autosomal recessively. Neurotoxic alpha-amino adipic semialdehyde (alpha-AASA), piperideine 6-carboxylate and pipecolic acid accumulate in body fluids. Neonatal or infantile onset seizures refractory to anti-epileptic medications are clinical features. Treatment with pyridoxine, arginine and lysine-restricted diet does not normalize neurodevelopmental outcome or accumulation of neurotoxic metabolites. There is no animal model for high throughput drug screening. For this reason, we developed and characterized the first knock-out aldh7a1 zebrafish model using CRISPR-Cas9 technology. Zebrafish aldh7a1 mutants were generated by using a vector free method of CRISPR-Cas9 mutagenesis. Genotype analysis of aldh7a1 knock-out zebrafish was performed by high resolution melt analysis, direct sequencing and QIAxcel system. Electroencephalogram was performed. Alpha-AASA, piperideine 6-carboxylate and pipecolic acid, were measured by liquid chromatography-tandem mass spectrometry. Our knock-out aldh7a1 zebrafish has homozygous 5 base pair (bp) mutation in ALDH7A1. Knock-out aldh7a1 embryos have spontaneous rapid increase in locomotion and a rapid circling swim behavior earliest 8-day post fertilization (dpf). Electroencephalogram revealed large amplitude spike discharges compared to wild type. Knock-out aldh7a1 embryos have elevated alpha-AASA, piperideine 6-carboxylate and pipecolic acid compared to wild type embryos at 3 dpf. Knock-out aldh7a1 embryos showed no aldh7a1 protein by western blot compared to wild type. Our knock-out aldh7a1 zebrafish is a well characterized model for large-scale drug screening using behavioral and biochemical features and accurately recapitulates the human PDE-ALDH7A1 disease.
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