eLife (Jun 2017)

Pilot study of large-scale production of mutant pigs by ENU mutagenesis

  • Tang Hai,
  • Chunwei Cao,
  • Haitao Shang,
  • Weiwei Guo,
  • Yanshuang Mu,
  • Shulin Yang,
  • Ying Zhang,
  • Qiantao Zheng,
  • Tao Zhang,
  • Xianlong Wang,
  • Yu Liu,
  • Qingran Kong,
  • Kui Li,
  • Dayu Wang,
  • Meng Qi,
  • Qianlong Hong,
  • Rui Zhang,
  • Xiupeng Wang,
  • Qitao Jia,
  • Xiao Wang,
  • Guosong Qin,
  • Yongshun Li,
  • Ailing Luo,
  • Weiwu Jin,
  • Jing Yao,
  • Jiaojiao Huang,
  • Hongyong Zhang,
  • Menghua Li,
  • Xiangmo Xie,
  • Xuejuan Zheng,
  • Kenan Guo,
  • Qinghua Wang,
  • Shibin Zhang,
  • Liang Li,
  • Fei Xie,
  • Yu Zhang,
  • Xiaogang Weng,
  • Zhi Yin,
  • Kui Hu,
  • Yimei Cong,
  • Peng Zheng,
  • Hailong Zou,
  • Leilei Xin,
  • Jihan Xia,
  • Jinxue Ruan,
  • Hegang Li,
  • Weiming Zhao,
  • Jing Yuan,
  • Zizhan Liu,
  • Weiwang Gu,
  • Ming Li,
  • Yong Wang,
  • Hongmei Wang,
  • Shiming Yang,
  • Zhonghua Liu,
  • Hong Wei,
  • Jianguo Zhao,
  • Qi Zhou,
  • Anming Meng

DOI
https://doi.org/10.7554/eLife.26248
Journal volume & issue
Vol. 6

Abstract

Read online

N-ethyl-N-nitrosourea (ENU) mutagenesis is a powerful tool to generate mutants on a large scale efficiently, and to discover genes with novel functions at the whole-genome level in Caenorhabditis elegans, flies, zebrafish and mice, but it has never been tried in large model animals. We describe a successful systematic three-generation ENU mutagenesis screening in pigs with the establishment of the Chinese Swine Mutagenesis Consortium. A total of 6,770 G1 and 6,800 G3 pigs were screened, 36 dominant and 91 recessive novel pig families with various phenotypes were established. The causative mutations in 10 mutant families were further mapped. As examples, the mutation of SOX10 (R109W) in pig causes inner ear malfunctions and mimics human Mondini dysplasia, and upregulated expression of FBXO32 is associated with congenital splay legs. This study demonstrates the feasibility of artificial random mutagenesis in pigs and opens an avenue for generating a reservoir of mutants for agricultural production and biomedical research.

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