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.

由于缺乏使用动物模型系统的适当实验方法，对生物体水平上 DNA 修复基因作用的系统了解受到限制。由于易于基因组编辑和大规模表型筛选，斑马鱼已成为一种强大的脊椎动物遗传模型系统。在这里，我们通过多重 CRISPR/Cas9 介导的诱变产生了 32 个 DNA 修复和复制基因的斑马鱼突变体。我们的突变体集合的大规模表型表征表明，三个基因（atad5a、ddb1 、 pcna）对于正常的胚胎发育和造血是必不可少的；七个基因（apex1，atrip，ino80，mre11a，shfm1、telo2、wrn）是幼年期生长发育所必需的，六个基因（blm、brca2、fanci 、 rad51、rad54l、rtel1）在性发育中起关键作用。此外，六个基因（atad5a、brca2、polk、rad51、shfm1、xrcc1）的突变显示出对 DNA 损伤剂的超敏反应。我们的斑马鱼突变体集合为了解 DNA 修复基因在有机体水平上的作用提供了独特的资源。