TY - JOUR TI - Precise base editing for the in vivo study of developmental signaling and human pathologies in zebrafish AU - Rosello, Marion AU - Vougny, Juliette AU - Czarny, François AU - Mione, Marina C AU - Concordet, Jean-Paul AU - Albadri, Shahad AU - Del Bene, Filippo A2 - Whitfield, Tanya T A2 - White, Richard M A2 - McGrail, Maura A2 - Balciunas, Darius VL - 10 PY - 2021 DA - 2021/02/12 SP - e65552 C1 - eLife 2021;10:e65552 DO - 10.7554/eLife.65552 UR - https://doi.org/10.7554/eLife.65552 AB - 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 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 disease-associated mutations. KW - base editors KW - CRISPR/Cas9 KW - animal models JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -