PUBLICATION

Large-scale generation and phenotypic characterization of zebrafish CRISPR mutants of DNA repair genes

Authors
Shin, U., Nakhro, K., Oh, C.K., Carrington, B., Song, H., Varshney, G.K., Kim, Y., Song, H., Jeon, S., Robbins, G., Kim, S., Yoon, S., Choi, Y.J., Kim, Y.J., Burgess, S., Kang, S., Sood, R., Lee, Y., Myung, K.
ID
ZDB-PUB-210815-5
Date
2021
Source
DNA repair   107: 103173 (Journal)
Registered Authors
Burgess, Shawn, Lee, Yoonsung, Sood, Raman, Varshney, Gaurav
Keywords
CRIPSR/Cas9, DNA damage sensitivity, DNA repair, Hematopoiesis, Multiplex mutagenesis, Sex development, Zebrafish
MeSH Terms
  • Animals
  • Gene Editing*
  • Zebrafish
PubMed
34390914 Full text @ DNA Repair (Amst).
Abstract
A systematic knowledge of the roles of DNA repair genes at the level of the organism has been limited due to the lack of appropriate experimental approaches using animal model systems. Zebrafish has become a powerful vertebrate genetic model system with availability due to the ease of genome editing and large-scale phenotype screening. Here, we generated zebrafish mutants for 32 DNA repair and replication genes through multiplexed CRISPR/Cas9-mediated mutagenesis. Large-scale phenotypic characterization of our mutant collection revealed that three genes (atad5a, ddb1, pcna) are essential for proper embryonic development and hematopoiesis; seven genes (apex1, atrip, ino80, mre11a, shfm1, telo2, wrn) are required for growth and development during juvenile stage and six genes (blm, brca2, fanci, rad51, rad54l, rtel1) play critical roles in sex development. Furthermore, mutation in six genes (atad5a, brca2, polk, rad51, shfm1, xrcc1) displayed hypersensitivity to DNA damage agents. Our zebrafish mutant collection provides a unique resource for understanding of the roles of DNA repair genes at the organismal level.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping