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
-
- Animals
- Disease Models, Animal
- Gene Editing
- Humans
- Mutation
- Oncogenes*
- Point Mutation*
- Signal Transduction*
- Zebrafish/metabolism
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- beta Catenin/genetics*
- beta Catenin/metabolism
- PubMed
- 33576334 Full text @ Elife
Citation
Rosello, M., Vougny, J., Czarny, F., Mione, M.C., Concordet, J.P., Albadri, S., Del Bene, F. (2021) Precise base editing for the in vivo study of developmental signaling and human pathologies in zebrafish. eLIFE. 10:.
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