Hai Tang, Cao Chunwei, Shang Haitao, Guo Weiwei, Mu Yanshuang, Yang Shulin, Zhang Ying, Zheng Qiantao, Zhang Tao, Wang Xianlong, Liu Yu, Kong Qingran, Li Kui, Wang Dayu, Qi Meng, Hong Qianlong, Zhang Rui, Wang Xiupeng, Jia Qitao, Wang Xiao, Qin Guosong, Li Yongshun, Luo Ailing, Jin Weiwu, Yao Jing, Huang Jiaojiao, Zhang Hongyong, Li Menghua, Xie Xiangmo, Zheng Xuejuan, Guo Kenan, Wang Qinghua, Zhang Shibin, Li Liang, Xie Fei, Zhang Yu, Weng Xiaogang, Yin Zhi, Hu Kui, Cong Yimei, Zheng Peng, Zou Hailong, Xin Leilei, Xia Jihan, Ruan Jinxue, Li Hegang, Zhao Weiming, Yuan Jing, Liu Zizhan, Gu Weiwang, Li Ming, Wang Yong, Wang Hongmei, Yang Shiming, Liu Zhonghua, Wei Hong, Zhao Jianguo, Zhou Qi, Meng Anming
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Chinese Swine Mutagenesis Consortium Working Group, Chinese Swine Mutagenesis Consortium, Beijing, China.
Elife. 2017 Jun 22;6:e26248. doi: 10.7554/eLife.26248.
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 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 (R109W) in pig causes inner ear malfunctions and mimics human Mondini dysplasia, and upregulated expression of 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.
N-乙基-N-亚硝基脲（ENU）诱变是一种强大的工具，可在果蝇、斑马鱼和小鼠中高效地大规模产生突变体，并在全基因组水平上发现具有新功能的基因，但从未在大型模式动物中尝试过。我们通过建立中国猪诱变联盟，成功地在猪中进行了系统性的三代ENU诱变筛选。共筛选了6770头G1猪和6800头G3猪，建立了36个具有各种表型的显性和91个隐性新猪家族。进一步定位了10个突变家族中的致病突变。例如，猪中的（R109W）突变导致内耳功能障碍，类似于人类蒙迪尼发育不全，而的表达上调与先天性叉腿有关。本研究证明了猪人工随机诱变的可行性，并为农业生产和生物医学研究生成突变体库开辟了一条途径。
