动物造模,血管性血友病小型猪模型 z-bio 2022-02-01 404

　　A research team led by Zhou Qi, a researcher at the Institute of Zoology, Chinese Academy of Sciences, used CRISPR/Cas9 technology to obtain vWF knockout pigs for the first time and established a miniature pig model of von Willebrand disease.

　　Pig is the most important livestock breed in my country, and it is also an important model animal in biomedical research. Pigs are closer to humans than rodents in many physiological characteristics of rodents (such as cardiovascular and gastrointestinal tract). The size and function of organs are very similar to humans, the litter is large, and they are easy to reproduce. On this basis, detailed genome modification of pigs to establish models for studying swine epidemics and human diseases is of great value to animal husbandry production and biomedical research.

　　CRISPR/Cas9 system is easy to construct and can rapidly mutate at multiple loci. Although it has been successful in animals such as rats and mice, it has not been applied to research on economic animals such as pigs. By directly injecting the CRISPR-Cas system that cuts the vWF gene into fertilized piglets, the research team effectively obtained surviving piglets with two allelic mutations and the applicability of CRISPR technology in large animals. Compared with the traditional "two-step method", the direct injection "one-step method" based on the efficiency and convenience of CRISPR. In the traditional "two-step method", the gene is first knocked out from the somatic cell, and then the gene is obtained through the somatic cell Knockout pig cell nuclear transfer, faster and more convenient to obtain gene knockout pigs. Mutations in vWF can cause clinical type I and type III von Willebrand disease. The study also found that the clinical phenotype of these knock-out pigs was similar to that of patients with von Willebrand disease: severe coagulation dysfunction. This is also the first report using CRISPR technology to create disease models for mammals with specific disease phenotypes. This research provides a new method that can quickly establish a transgenic animal model of pigs, and greatly promotes the research on the etiology and treatment of livestock and human diseases.

　　This research was supported by the Stem Cell and Regenerative Medicine Strategic Science and Technology Experiment Project of the Chinese Academy of Sciences, the major scientific research project of the Ministry of Science and Technology, and the National Natural Science Foundation of China.