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Article Dans Une Revue eLife Année : 2021

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

Résumé

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-toT 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 ctnnb1 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 cbl. 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 diseaseassociated mutations.
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Origine : Publication financée par une institution

Dates et versions

hal-03184313 , version 1 (29-03-2021)

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Marion Rosello, Juliette Vougny, François Czarny, Marina Mione, Jean-Paul Concordet, et al.. Precise base editing for the in vivo study of developmental signaling and human pathologies in zebrafish. eLife, 2021, 10, ⟨10.7554/elife.65552⟩. ⟨hal-03184313⟩
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