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Precise base editing for the in vivo study of developmental signaling and human pathologies in zebrafish

eLife, 2021-02, Vol.10 [Peer Reviewed Journal]

2021, Rosello et al. ;COPYRIGHT 2021 eLife Science Publications, Ltd. ;2021, Rosello et al. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;Distributed under a Creative Commons Attribution 4.0 International License ;2021, Rosello et al 2021 Rosello et al ;ISSN: 2050-084X ;EISSN: 2050-084X ;DOI: 10.7554/eLife.65552 ;PMID: 33576334

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Title:
Precise base editing for the in vivo study of developmental signaling and human pathologies in zebrafish
Author: Rosello, Marion ; Vougny, Juliette ; Czarny, François ; Mione, Marina C ; Concordet, Jean-Paul ; Albadri, Shahad ; Del Bene, Filippo
Subjects: animal models ; Animals ; base editors ; beta Catenin - genetics ; beta Catenin - metabolism ; Cell signaling ; Cellular signal transduction ; CRISPR ; CRISPR/Cas9 ; CTNNB1 gene ; Danio rerio ; Developmental Biology ; Disease Models, Animal ; Dwarfism ; Efficiency ; Embryos ; Gene Editing ; Gene mutations ; Genes ; Genetic aspects ; Genetic disorders ; Genetic engineering ; Genetics and Genomics ; Genomes ; Humans ; Life Sciences ; Medical research ; Medicine, Experimental ; Mimicry ; Mutation ; Oncogenes ; Point Mutation ; Retina ; Signal Transduction ; Tools and Resources ; Wnt protein ; Zebrafish ; Zebrafish - metabolism ; Zebrafish Proteins - genetics ; Zebrafish Proteins - metabolism
Is Part Of: eLife, 2021-02, Vol.10
Description: While zebrafish is emerging as a new model system to study human diseases, an efficient methodology to generate precise point mutations at high efficiency is still lacking. Here we show that base editors can generate C-to-T point mutations with high efficiencies without other unwanted on-target mutations. In addition, we established a new editor variant recognizing an NAA protospacer adjacent motif, expanding the base editing possibilities in zebrafish. Using these approaches, we first generated a base change in the gene, mimicking oncogenic an mutation of the human gene known to result in constitutive activation of endogenous Wnt signaling. Additionally, we precisely targeted several cancer-associated genes including . With this last target, we created a new zebrafish dwarfism model. Together our findings expand the potential of zebrafish as a model system allowing new approaches for the endogenous modulation of cell signaling pathways and the generation of precise models of human genetic disease-associated mutations.
Publisher: England: eLife Science Publications, Ltd
Language: English
Identifier: ISSN: 2050-084X
EISSN: 2050-084X
DOI: 10.7554/eLife.65552
PMID: 33576334
Source: Hyper Article en Ligne (HAL) (Open Access)
MEDLINE
DOAJ (Directory of Open Access Journals)
PubMed Central
ROAD: Directory of Open Access Scholarly Resources
ProQuest Central

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Precise base editing for the in vivo study of developmental signaling and human pathologies in zebrafish

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