【Animal Experiment】-Successfully bred immunodeficiency rabbits with TALENs gene knockout technology
动物实验,免疫缺陷
z-bo
2020-08-13
602
The research team led by Dr. Liangxue Lai and Dr. Duanqing Pei of the Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences applied the transcription activator-like effector nuclease (TALENs) technology to the study of rabbit gene knockout and established an efficient platform for rabbit gene targeting. And using this technology platform to successfully knock out the recombination activation gene (RAG) responsible for the rearrangement of T cells and B cells, and establish the world's first immunodeficiency rabbit disease model. The results were published online on July 9 in the International Journal On Cell Research.
The rabbit is an important experimental animal. The targeted modification of some of its genetic characteristics can greatly expand the application value of the rabbit in the field of biomedicine research. However, because the rabbit embryonic stem cell line with germline chimerism has not been established in the world, the cloning efficiency of rabbits is extremely low, and it is extremely difficult to obtain gene knockout rabbits and the efficiency is extremely low. At present, there is only one case of gene knockout rabbit reported in the world. The recently emerged TALEN technology has been proven in other animals to be an efficient and simple genetic modification technology. Through exploration, the research team has opened up the technical route of TALENs for gene targeting in rabbits. In the knockout experiments on the RAG gene, the gene knockout efficiency reached more than 90%, and the biallelic knockout efficiency reached more than 60%. The establishment of TALEN-mediated high-efficiency gene targeting technology platform has cleared the technical obstacles for large-scale targeted genetic modification of rabbits.
The research team used TALEN technology to successfully knock out the RAG gene, which caused the development of T cells and B cells to be blocked. Therefore, the obtained RAG gene knockout rabbits lost most of their immune functions, thus cultivating the world's first immune system. Defective rabbit model. This achievement provides an important animal model for biomedical research including the pathogenesis of human-related diseases (such as Omenn syndrome), drug development, organ transplantation research, and stem cell research.
The research was funded by the National Science and Technology Major Special Project for the Prevention and Treatment of Major Infectious Diseases such as AIDS and Viral Hepatitis.