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*
  • Disease Models, Animal
  • Point Mutation*
  • Mutation
  • Humans
  • Zebrafish/metabolism
  • Signal Transduction*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
(all 13)
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
Figures
Figure Gallery (4 images)
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Expression
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Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ia4TgTransgenic Insertion
    idv2
      MNV
      1 - 2 of 2
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      Human Disease / Model
      Human Disease Fish Conditions Evidence
      Noonan syndromecblidv2/idv2standard conditionsTAS
      1 - 1 of 1
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      Sequence Targeting Reagents
      Fish
      1 - 2 of 2
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      Antibodies
      No data available
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      GFPEFGGFP
      1 - 1 of 1
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      Mapping
      No data available