动物造模,严重联合免疫缺陷动物模型 z-bio 2021-10-14 710

　　(1) SCID mouse model SCID mouse is a kind of congenital T and B lymphocyte immunodeficiency animal. It was found to be homozygous with C.B-17, caused by a single recessive mutant gene located on the scid on chromosome 16. The homozygous scid gene causes abnormal recombinase activity, which regulates the coding sequence of the lymphocyte antigen receptor gene VDJ, rearranges the VDJ region and prevents the normal connection of the bifurcated ends. After the rearrangement, the antigen receptor gene is deleted, resulting in T and B abnormalities. The cells themselves cannot differentiate into specific functional lymphocytes. CB-17 and BALB/cAnlcr are inbred strains of the same species. CB-17 mutant SCID mice (CB-17scid/scid), because in addition to the mouse C57BL/ka immunoglobulin heavy chain Igh-1b allele (different from BALB/cAnlcr and BALB), the other two kinds of mice The genes are exactly the same. /cAnlcr has basically the same genetic background, and their H-2 antigens are all H-2d. In addition, SCID mice with genetic background have emerged, such as C3H-scid and other mouse strains. The appearance of SCID mice is the same as that of normal mice, and their body weight is normal, but the weight of thymus, spleen and lymph nodes is less than 30% of normal mice, and histology shows obvious lack of lymphocytes. .. The thymus is surrounded by adipose tissue and has no cerebral cortex structure. Only the medulla oblongata remains. It is mainly composed of epithelial cell-like nuclear fibroblasts, with local lymphocytes visible at the edges. The white serum in the spleen is not clear, the red serum is normal, and there is no lymphocyte accumulation in the spleen. Lymph nodes are mainly composed of reticulocytes. There is no obvious cortical area. There is no cortical area. There are lymphocytes. It is hollowed out and occupied by reticulate cells. The submucosal and bronchial lymph nodes of the small intestine are sparse, and there is no accumulation of lymphocytes in the structure. The bone marrow structure is normal. There are few white blood cells in peripheral blood, and lymphocytes account for 10% to 20% of the total number of white blood cells, while normal mice should account for about 70%. All T lymphocyte and B lymphocyte function tests in SCID mice are negative, have no antibody response to cell-mediated immunity and foreign antigens, and lack cells that carry pre-B, B and T cell surface markers. However, the differentiation of lymphohematopoietic cells is not affected by the mutant gene, and macrophages, granulocytes, megakaryocytes, red blood cells, etc. are in a normal state. The extracellular fluid activated by K cells and lymphokines is normal.

　　(2) NOD/SCID mice

　　non-obese diabetes (non-obese diabetes, NOD) mice are widely used autoimmune type 1 diabetes. This is a study by Japanese scholars on non-self-bred Jcl:ICR mice. -Obese diabetic strains have been isolated from sub-families that are susceptible to cataracts. In the 20th generation of inbreds, it was found that 60% to 80% of female NOD mice and 20% to 30% of male mice could spontaneously develop insulin-dependent diabetes. Type 1 diabetes is an autoimmune disease mediated by T cells, in which lymphocytes play an important role in mediating specific damage to pancreatic B cells. When the body's immune system becomes unregulated, it causes the activation and proliferation of autoreactive T cells targeting pancreatic β cells, destroying β cells and causing diabetes. By putting

　　The SCID mutant gene was introduced into NOD, combined with the immunodeficiency of T lymphocytes and B lymphocytes, reduced NK cell activity, lack of circulating complement, and impaired functions of macrophages and antigen-presenting cells, thus obtaining NOD/SCID. Mouse. It is one of the ideal research models for human tumor xenotransplantation.

　　(3) NOG, NPG mouse

　　The full name of

　　OG mouse is NODShi.Cg-PrkdcscidIl2rgtmlSug/Jic, which was successfully bred in 2000 by the Central Laboratory of Laboratory Animal Research (CIEA) of Japan. The mouse is a NOD/SCID mouse. As a genetic background, the IL-2 receptor protein γ chain gene (IL-2rYnull) was deleted. Since then, the Jackson Laboratory of the United States proposed a similar immunodeficiency mouse NOG.Cg-PrkdcscidIl2rgtmlWjl/SzJ and named it NPG mouse. The γ chain of the IL-2 receptor is the co-receptor subunit of the cytokines IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21, and has important immune functions. . After gene knockout, the immune function of the human body is significantly reduced, especially the activity of NK cells is greatly lost. Therefore, NOG or NPG mice lack both T and B lymphocytes and functional NK cells, making it the most immunodeficient mouse model in the world so far, and the best mouse model in the world, and it is also considered It is a human xenotransplantation. Receptor. Currently, this type of mouse is widely used in the study of humanized models of hematopoiesis, immunity, drugs, viruses, and tumors.

　　(4) Motheaten mouse model

　　Motheaten mouse model mutant gene (me) is located on the 6th pair of chromosomes, skin abscesses can appear within 2 hours of age, severe combined immunodeficiency, and dependence on the thymus. Regardless of the antigen, there is no response, significantly weakening the proliferative response to T and B cytokinins, and reducing cytotoxicity and NK cell activity. Homozygotes (me/me) also have autoimmune tendencies, and immune complexes can be deposited in the kidneys, lungs and skin. The mouse of this strain is an important model for distinguishing the immune dysfunction in early life and the development of certain autoimmune diseases. Artificially reared mice with congenital complex immunodeficiency: Three recessive mutant genes are distributed in three types of mice: beige genes lacking in NK cells, nu genes lacking in T cells, and certain xid genes lacking in B cells. Cross and filter. Introduce and breed beige nude mice with triple immunodeficiency of T cells, B cells and NK cells. In addition, in CBA/N-nu mice, when the nude mouse gene (nu) is introduced into CBA/N mice, the functions of mouse T cells and B cells are defective.