ArticlePloS one2018
Acute multi-sgRNA knockdown of KEOPS complex genes reproduces the microcephaly phenotype of the stable knockout zebrafish model.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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.
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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.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- OSGEP, A Negative Ferroptotic Regulator, Alleviates Cerebral Ischemia-Reperfusion Injury Through Modulating mNeurochemical research · 2025Article
- O-sialoglycoprotein Endopeptidase (OSGEP) Suppresses Hepatic Ischemia-Reperfusion Injury-Induced Ferroptosis Through Modulating the MEK/ERK Signaling Pathway.Molecular biotechnology · 2025Article
- Structures of KEOPS bound to tRNA reveal functional roles of the kinase Bud32.Nature communications · 2024Article
- Molecular basis of A. thaliana KEOPS complex in biosynthesizing tRNA t6A.Nucleic acids research · 2024Article
- Modelling human lower urinary tract malformations in zebrafish.Molecular and cellular pediatrics · 2023Review
- Susceptibility and Permissivity of Zebrafish (Viruses · 2023Article
- The structural and functional workings of KEOPS.Nucleic acids research · 2021Review
- CRISPR gRNA phenotypic screening in zebrafish reveals pro-regenerative genes in spinal cord injury.PLoS genetics · 2021Article
- Drug Screening with Genetically Encoded Fluorescent Sensors: Today and Tomorrow.International journal of molecular sciences · 2020Review
- LGR4 deficiency results in delayed puberty through impaired Wnt/β-catenin signaling.JCI insight · 2020Article
- Modeling Neuronal Diseases in Zebrafish in the Era of CRISPR.Current neuropharmacology · 2020Review
- Bi-allelic Variants in METTL5 Cause Autosomal-Recessive Intellectual Disability and Microcephaly.American journal of human genetics · 2019Article
- Corticosteroid treatment exacerbates nephrotic syndrome in a zebrafish model of magi2a knockout.Kidney international · 2019Article
- Combining Zebrafish and CRISPR/Cas9: Toward a More Efficient Drug Discovery Pipeline.Frontiers in pharmacology · 2018Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Until recently, morpholino oligonucleotides have been widely employed in zebrafish as an acute and efficient loss-of-function assay. However, off-target effects and reproducibility issues when compared to stable knockout lines have compromised their further use. Here we employed an acute CRISPR/Cas approach using multiple single guide RNAs targeting simultaneously different positions in two exemplar genes (osgep or tprkb) to increase the likelihood of generating mutations on both alleles in the injected F0 generation and to achieve a similar effect as morpholinos but with the reproducibility of stable lines. This multi single guide RNA approach resulted in median likelihoods for at least one mutation on each allele of >99% and sgRNA specific insertion/deletion profiles as revealed by deep-sequencing. Immunoblot showed a significant reduction for Osgep and Tprkb proteins. For both genes, the acute multi-sgRNA knockout recapitulated the microcephaly phenotype and reduction in survival that we observed previously in stable knockout lines, though milder in the acute multi-sgRNA knockout. Finally, we quantify the degree of mutagenesis by deep sequencing, and provide a mathematical model to quantitate the chance for a biallelic loss-of-function mutation. Our findings can be generalized to acute and stable CRISPR/Cas targeting for any zebrafish gene of interest.
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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.