PUBLICATION
Precise base editing for the in vivo study of developmental signaling and human pathologies in zebrafish
- Authors
- Rosello, M., Vougny, J., Czarny, F., Mione, M.C., Concordet, J.P., Albadri, S., Del Bene, F.
- ID
- ZDB-PUB-210213-18
- Date
- 2021
- Source
- eLIFE 10: (Journal)
- Registered Authors
- Del Bene, Filippo, Mione, Marina, Rosello, Marion
- Keywords
- developmental biology, genetics, genomics, zebrafish
- MeSH Terms
-
- beta Catenin/genetics*
- beta Catenin/metabolism
- Gene Editing
- Animals
- Oncogenes*
- PubMed
- 33576334 Full text @ Elife
Abstract
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 PAM, expanding the base editing possibilities in zebrafish. Using these approaches, we first generated a base change in the ctnnb1 gene, mimicking oncogenic mutations 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping