1. Developmental Biology
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A pilot study of large-scale production of mutant pigs by ENU mutagenesis

  1. Tang Hai
  2. Chunwei Cao
  3. Haitao Shang
  4. Weiwei Guo
  5. Yanshuang Mu
  6. Shulin Yang
  7. Ying Zhang
  8. Qiantao Zheng
  9. Tao Zhang
  10. Xianlong Wang
  11. Yu Liu
  12. Qingran Kong
  13. Kui Li
  14. Dayu Wang
  15. Meng Qi
  16. Qianlong Hong
  17. Rui Zhang
  18. Xiupeng Wang
  19. Qitao Jia
  20. Xiao Wang
  21. Guosong Qin
  22. Yongshun Li
  23. Ailing Luo
  24. Weiwu Jin
  25. Jing Yao
  26. Jiaojiao Huang
  27. Hongyong Zhang
  28. Menghua Li
  29. Xiangmo Xie
  30. Xuejuan Zheng
  31. Kenan Guo
  32. Qinhua Wang
  33. Shibin Zhang
  34. Liang Li
  35. Fei Xie
  36. Yu Zhang
  37. Xiaogang Weng
  38. Zhi Yin
  39. Kui Hu
  40. Yimei Cong
  41. Peng Zheng
  42. Hailong Zou
  43. Leilei Xin
  44. Jihan Xia
  45. Jinxue Ruan
  46. Hegang Li
  47. Weiming Zhao
  48. Jing Yuan
  49. Zizhan Liu
  50. Weiwang Gu
  51. Ming Li
  52. Yong Wang
  53. Hongmei Wang  Is a corresponding author
  54. Shiming Yang  Is a corresponding author
  55. Zhonghua Liu  Is a corresponding author
  56. Hong Wei  Is a corresponding author
  57. Jianguo Zhao  Is a corresponding author
  58. Qi Zhou  Is a corresponding author
  59. Anming Meng  Is a corresponding author
  1. Institute of Zoology, Chinese Academy of Sciences, China
  2. Third Military Medical University, China
  3. Chinese PLA General Hospital, China
  4. Northeast Agricultural University of China, China
  5. Chinese Academy of Agricultural Sciences, China
  6. College of Life Science, China
  7. Pearl Laboratory Animal Sci. & Tech. Co. Ltd, China
  8. Tsinghua University, China
Research Article
  • Cited 21
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Cite this article as: eLife 2017;6:e26248 doi: 10.7554/eLife.26248

Abstract

N-ethyl-N-nitrosourea (ENU) mutagenesis is a powerful tool to efficiently generate large scale of mutants and discover genes with novel functions at the whole-genome level in C. elegans, flies, zebrafish and mice, but has never been tried in large model animals. In the current study, we reported a successful systematic three-generation ENU mutagenesis screening in pigs with the establishment of 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 up-regulated 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 agriculture production and biomedicine research.

Article and author information

Author details

  1. Tang Hai

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  2. Chunwei Cao

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  3. Haitao Shang

    Department of Laboratory Animal Science, College of Basic Medicine, Third Military Medical University, Chongqing, China
    Competing interests
    The authors declare that no competing interests exist.

  4. Weiwei Guo

    Department of Otolaryngology-Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  5. Yanshuang Mu

    College of Life Science, Northeast Agricultural University of China, Harbin, China
    Competing interests
    The authors declare that no competing interests exist.

  6. Shulin Yang

    Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  7. Ying Zhang

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  8. Qiantao Zheng

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  9. Tao Zhang

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  10. Xianlong Wang

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  11. Yu Liu

    Department of Laboratory Animal Science, College of Basic Medicine, Third Military Medical University, Chongqin, China
    Competing interests
    The authors declare that no competing interests exist.

  12. Qingran Kong

    College of Life Science, Northeast Agricultural University of China, Harbin, China
    Competing interests
    The authors declare that no competing interests exist.

  13. Kui Li

    Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  14. Dayu Wang

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  15. Meng Qi

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  16. Qianlong Hong

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  17. Rui Zhang

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  18. Xiupeng Wang

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  19. Qitao Jia

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  20. Xiao Wang

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  21. Guosong Qin

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  22. Yongshun Li

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  23. Ailing Luo

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  24. Weiwu Jin

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  25. Jing Yao

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  26. Jiaojiao Huang

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  27. Hongyong Zhang

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  28. Menghua Li

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  29. Xiangmo Xie

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  30. Xuejuan Zheng

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijng, China
    Competing interests
    The authors declare that no competing interests exist.

  31. Kenan Guo

    Department of Laboratory Animal Science, College of Basic Medicine, Third Military Medical University, Chongqin, China
    Competing interests
    The authors declare that no competing interests exist.

  32. Qinhua Wang

    Department of Laboratory Animal Science, College of Basic Medicine, Third Military Medical University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  33. Shibin Zhang

    Department of Laboratory Animal Science, College of Basic Medicine, Third Military Medical University, Chongqing, China
    Competing interests
    The authors declare that no competing interests exist.

  34. Liang Li

    Department of Laboratory Animal Science, College of Basic Medicine, Third Military Medical University, Chongqing, China
    Competing interests
    The authors declare that no competing interests exist.

  35. Fei Xie

    Department of Laboratory Animal Science, College of Basic Medicine, Third Military Medical University, Chongqing, China
    Competing interests
    The authors declare that no competing interests exist.

  36. Yu Zhang

    College of Life Science, Northeast Agricultural University of China, Harbin, China
    Competing interests
    The authors declare that no competing interests exist.

  37. Xiaogang Weng

    College of Life Science, Northeast Agricultural University of China, Harbin, China
    Competing interests
    The authors declare that no competing interests exist.

  38. Zhi Yin

    College of Life Science, Northeast Agricultural University of China, Harbin, China
    Competing interests
    The authors declare that no competing interests exist.

  39. Kui Hu

    Northeast Agricultural University of China, College of Life Science, Harbin, China
    Competing interests
    The authors declare that no competing interests exist.

  40. Yimei Cong

    College of Life Science, Northeast Agricultural University of China, Harbin, China
    Competing interests
    The authors declare that no competing interests exist.

  41. Peng Zheng

    College of Life Science, Northeast Agricultural University of China, Harbin, China
    Competing interests
    The authors declare that no competing interests exist.

  42. Hailong Zou

    College of Life Science, Northeast Agricultural University of China, Harbin, China
    Competing interests
    The authors declare that no competing interests exist.

  43. Leilei Xin

    Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  44. Jihan Xia

    Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  45. Jinxue Ruan

    Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  46. Hegang Li

    Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  47. Weiming Zhao

    Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  48. Jing Yuan

    Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  49. Zizhan Liu

    Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  50. Weiwang Gu

    Pearl Laboratory Animal Sci. & Tech. Co. Ltd, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.

  51. Ming Li

    Pearl Laboratory Animal Sci. & Tech. Co. Ltd, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.

  52. Yong Wang

    Department of Laboratory Animal Science, College of Basic Medicine, Third Military Medical University, Chongqing, China
    Competing interests
    The authors declare that no competing interests exist.

  53. Hongmei Wang

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijng, China
    For correspondence
    wanghm@ioz.ac.cn
    Competing interests
    The authors declare that no competing interests exist.

  54. Shiming Yang

    Department of Otolaryngology-Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China
    For correspondence
    yangsm301@263.net
    Competing interests
    The authors declare that no competing interests exist.

  55. Zhonghua Liu

    College of Life Science, Northeast Agricultural University of China, Harbin, China
    For correspondence
    liu086@126.com
    Competing interests
    The authors declare that no competing interests exist.

  56. Hong Wei

    Department of Laboratory Animal Science, College of Basic Medicine, Third Military Medical University, Chongqing, China
    For correspondence
    weihong63528@163.com
    Competing interests
    The authors declare that no competing interests exist.

  57. Jianguo Zhao

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    For correspondence
    zhaojg@ioz.ac.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6587-4823

  58. Qi Zhou

    State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    For correspondence
    qzhou@ioz.ac.cn
    Competing interests
    The authors declare that no competing interests exist.

  59. Anming Meng

    School of Life Sciences, Tsinghua University, Beijing, China
    For correspondence
    mengam@mail.tsinghua.edu.cn
    Competing interests
    The authors declare that no competing interests exist.

Funding

Ministry of Science and Technology of the People's Republic of China (National Basic Research Program of China)

  • Jianguo Zhao

National Natural Science Foundation of China (National High Technology Research and Development Program of China)

  • Jianguo Zhao

Chinese Academy of Sciences (Strategic Priority Research Program of CAS)

  • Jianguo Zhao

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All experiments involving animals were performed according to the protocols approved by the Institutional Animal Care and Use Committee of the Institute of Zoology, Chinese Academy of Sciences, China. All surgery was performed under sodium pentobarbital anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Hong Zhang, Institute of Biophysics, Chinese Academy of Sciences, China

Publication history

  1. Received: February 23, 2017
  2. Accepted: June 15, 2017
  3. Accepted Manuscript published: June 22, 2017 (version 1)
  4. Version of Record published: July 11, 2017 (version 2)
  5. Version of Record updated: July 17, 2017 (version 3)

Copyright

© 2017, Hai et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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