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