动物造模,基因敲除免疫缺陷 z-bio 2021-12-02 501

　　The research team of Dr. Lai Liangxue, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, successfully used TALEN technology to knock out the RAG gene in miniature pigs and obtained a severe combined immunodeficiency miniature pig model.

　　The main members of the team, Dr. Huaqiang Yang and Dr. Jiao Huang, designed TALEN plasmid pairs for the exons of RAG1 and RAG2 of pigs respectively, and obtained heterozygous and homozygous RAG1/2 knockouts after transfection of pig fetal fibroblasts Cell clone. Cell clones were used for somatic cell nuclear transfer to obtain 27 cloned pigs, of which 10 were RAG2 biallelic base deletions, 9 were RAG1 biallelic base deletions, and 3 were RAG2 biallelic base deletions. All base deletions caused a frame shift of the exon reading frame. RAG1/2 biallelic knockout pigs showed typical features of Severe combined immunodeficiency disease (SCID), including thymus atrophy, splenic dysplasia, lymphopenia, and somatic genome V(D)J heavy The row disappeared, and there were no mature T and B cells.

　　Immunodeficiency animals refer to animals that are genetically modified or artificially cause one or more immune system components to be defective. Severe combined immunodeficiency disease, that is, SCID mice are widely used to infect immunity, inflammation, tumors, and stem cells. Related research. However, mice are quite different from humans in body size, life span, and immune response mechanisms to inflammation, and are limited in research related to human clinical such as vaccine development, drug screening and clinical evaluation, and long-term follow-up of stem cell therapy. Since pigs are similar to humans in body size, life span, physiological indicators, especially immune mechanisms, the SCID miniature pig model with RAG knockout successfully established in this study is expected to play an important role in biomedicine and translational medicine.