Programmable base editing in zebrafish using a modified CRISPR-Cas9 system

Methods. 2018 Nov 1:150:19-23. doi: 10.1016/j.ymeth.2018.07.010. Epub 2018 Aug 2.

Abstract

The use of CRISPR/Cas9 to knockout genes in zebrafish has been well established. However, to better model many human diseases that are caused by point mutations, a robust methodology for generating desirable DNA base changes is still needed. Recently, Cas9-linked cytidine deaminases (base editors) evolved as a strategy to introduce single base mutations in model organisms. They have been used to convert cytidine to thymine at specific genomic loci. Here we describe a protocol for using the base editing system in zebrafish and its application to reproduce a single base mutation observed in human Ablepharon-Macrostomia Syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics
  • Animals
  • Base Sequence / genetics
  • CRISPR-Cas Systems / genetics*
  • Cytidine / metabolism
  • Cytidine Deaminase / genetics
  • Disease Models, Animal
  • Embryo, Nonmammalian
  • Eye Abnormalities / genetics
  • Female
  • Gene Editing / methods*
  • Humans
  • Macrostomia / genetics
  • Male
  • Mutagenesis, Site-Directed / methods
  • Point Mutation / genetics
  • RNA, Guide, CRISPR-Cas Systems
  • Thymine / metabolism
  • Twist-Related Protein 2 / genetics
  • Zebrafish / genetics*
  • Zebrafish Proteins / genetics

Substances

  • RNA, Guide, CRISPR-Cas Systems
  • Twist-Related Protein 2
  • Zebrafish Proteins
  • Cytidine
  • Cytidine Deaminase
  • Thymine

Supplementary concepts

  • Ablepharon macrostomia syndrome