免疫缺陷小鼠,动物造模 z-bio 2022-01-05 785

　　The establishment of highly immunodeficient mice provides important tools and guarantees for the clinical treatment of human tumors. So what does an immunodeficient mouse mean? What is a category? Why are B-NSG mice the weakest mice? I want to talk about the following three issues. There are some shortcomings, so please correct and add.

　　1) What does immunodeficient mice mean? As the name suggests,

　　"　" refers to immunodeficient mice. Some areas of expertise are due to the development, differentiation and growth of immune cells. Any part or component of the immune system is due to congenital hypoplasia or abnormal metabolism caused by a variety of factors, which refers to abnormal immune function.

　　2) What kind of immunodeficient mice do you have? According to different methods of obtaining congenital (or secondary) immunodeficiency mice, they can be divided into two types. Acquired (or secondary) immunodeficiency mice are usually immunodeficient mice due to some acquired causes (malnutrition, malignant tumors, drugs, viruses, etc.), although the original genes are still available. The scope of the acquisition is too wide, so if you are interested, please learn by yourself first and share it after understanding. For mice with congenital immunodeficiency, here is a comprehensive introduction to some of the resources I have seen. Congenital (or primary) immunodeficiency mice have genetic defects that can lead to a high degree of sensitivity to pathogenic microorganisms. According to the type of lost immune cells, they can also be divided into five categories: a) Mice with defective T lymphocyte function (such as nude mice) Nude mice: congenital thymus. The naked gene is a recessive mutant gene on chromosome 11. The naked genes are backcrossed to different mouse strains through genetic reproduction. In other words, they were introduced into different genetic backgrounds. Including NIH-nu, BALB/c-nu, C3H-nu, C57BL/6-nu, etc. Therefore, the performance of the cell-mediated immune response is different from laboratory experimental indicators. B) B-lymphocyte-deficient mice (for example, sex-related immunodeficiency mice CBA/N mice) CBA/N mice: B cell defects on the X sex chromosome, the gene symbol xid. CBA/N mice lack humoral immune response to thymus-independent type II antigens, reduce serum IgM and IgG levels, have no response to B cell mitogens, and have a large number of B cells secreting IgM and IgG subclasses. Decrease, its T cell function is normal. CBA/N mice can be repaired by bone marrow transplantation, making them ideal animals for studying the production, function and heterogeneity of B lymphocytes. Its pathology is related to human Bruton's gamma globulin deficiency and Weskard Edersh syndrome. This is an ideal model.

　　C) Mice with defective NK cell function (eg beige mice)

　　Beige mice: Beige mice are mutant mice with defective NK cell activity and develop a recessive inheritance of bg on chromosome 13. Mice. bg/bg) has a complete coat and light coat colors. The lack of endogenous NK cell function is due to the destruction of the cognitive process of cell lysis. The homozygous bg gene damages the function of cytotoxic T cells, reduces the chemotaxis and bactericidal activity of granulocytes, delays the anti-tumor killing effect of macrophages, destroys lysosome membranes, and impairs lysosome function. It is more sensitive to various virulence factors, so it needs an SPF environment. D) Combined immunodeficient mice can be understood as mice with combined defects of T, B and NK cells. For example, T and B cell combined immunodeficiency mice (SCID mice);

　　"T, NK cell deficient mice, T, B, NK cell triple immunodeficiency mice (B-NSG mice), etc.

　　SCID mouse: SCID mouse He has a white coat and is developing normally. However, the weight of the thymus, spleen and lymph nodes is less than 30% of normal body weight, and the histological symptoms of lymphocytes are obviously insufficient. The thymus is surrounded by multiple adipose tissues without cortical structure, leaving only the medulla oblongata. The medulla oblongata is mainly composed of epithelioid synthetic fibroblasts with local lymphocytes at the end. The white pulp of the spleen is unclear, the red pulp is normal, and the spleen lacks the accumulation of lymphocytes and is mainly composed of reticulocytes. There is no obvious cortical area in the lymph nodes, and the gluten cortex area is missing and occupied by reticulocytes. The submucosal and bronchial lymph nodes of the small intestine are sparse, and there is no accumulation of lymph nodes in the structure. SCID mice are extremely susceptible to infection and can survive in a very clean SPF environment of 3-5 litters for more than one year. SCID mice are another highly valuable immunodeficiency animal discovered by humans after the emergence of nude mice.

　　E) Other immunodeficiency mice-the dominant semilipid mouse dominant mutant gene Dh is a dominant mutant gene located on chromosome 1, which is homozygous for serious malformations of the genitourinary system and skeletal system. spleen. , Humoral immunity, genitourinary system, gastrointestinal tract and bones have certain deformities. There are no special breeding conditions for this kind of mice. The combination of u and Dh genes can be used to breed La-sat mice with thymus and spleen.