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As an important animal, pigs are not only the main source of human meat, but also an indispensable model animal in biomedical research.
the lack of functional genes hinders the development of genetic modification of pig's economic features, as well as the creation of large animal models of human genetic diseases.
screening mutants through artificial mutagenics is an important means to discover new functional genes and study their function.
artificial mutagenic online worms, fruit flies, zebrafish and mice have been shown to be an effective way to obtain genetic mutations and alter biological conditions, and have won several Nobel Prizes.
but artificial mutagement is still blank in the study of large animals. ENU (N-ethyl-N-nitrosamine), the most widely used in
artificial mutagenics, is a chemical mutant that can randomly induce the production of point mutations in the genome rather than the loss of large fragments, thus achieving large-scale creation of mutants and mining of new genes.
At the initiative of Meng Anming and Zhou Qi, academicians of the Chinese Academy of Sciences, Meng Anming, Zhou Qi, Zhao Jianguo and Wang Hongmei of the Institute of Zoology of the Chinese Academy of Sciences joined forces with Wei Wei, a professor at the Third Military Medical University, Liu Zhonghua, a professor at Northeastern Agricultural University, and Yang Shiming, a researcher at the PLA General Hospital. Li Kui, Yang Shulin, a researcher at the Beijing Institute of Livestock and Veterinary Research of the Chinese Academy of Agricultural Sciences, and Gu Weiwang, a professor at Southern Medical University, set up the "China Pig Chemical Mutagenic Alliance", successfully established a chemical mutagenic system for pigs, and carried out large-scale research on chemical mutagenic and mutant screening of pigs ENU.
in a paper published online June 22 by eLife, the alliance's member units first established a chemical mutagenic system for Guangxi Bama pigs, building a three-generation genetic family of explicit and recessive mutants.
through the large-scale screening of 6770 G1 and 6800 G3 mutagenic groups, 36 explicit genetic mutants and 91 recessive genetic mutants were successfully obtained, and a number of large animal models and breeding materials that can accurately simulate human diseases were established.
One of the mutants of endot ear malformation is highly similar to the pathological dedicate of human Mondini endotinosis disease, and its pathogenic location is precisely positioned as a change in amino acid number 109 of the SOX10 gene (R109W).
the mutant could be used as the first large animal model of human Mondini endometle disease, suggesting that the SOX10 gene may be the pathogenic gene for Mondini inner ear malformation.
addition, a study of the family of post-paralysis mutants has found that an increase in the negative regulatory factor FBXO32 gene in muscles can cause muscle atrophy and lead to post-limb paralysis.
For the first time, the study accelerated the frequency of mutations in pig endogenic genes through ENU chemical mutagenics, and large-scale preparation of mutants in large animals, promoted the development of pigs as model animals, and provided a new strategy for the cultivation of new breeds of pigs and the establishment of large animal models for clinical diseases.
the study was completed with the support of the Chinese Academy of Sciences' Strategic Pilot Special Project, the National Science and Technology Major Special Project for the Cultivation of New Varieties of Genetically Modified Organisms, the Ministry of Science and Technology "973", "863" and the National Natural Fund Commission.
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