动物造模,细胞人源化动物模型 z-bio 2021-05-24 344

　　Laboratory animals are important tools and supporting platforms for life science and biomedical research and development. Among them, mice are the most important experimental animals for studying genetic functions and human diseases. However, there are still many differences between human and mouse gene and protein sequences. Many human proteins cannot combine with mouse homologous proteins to produce biological activity. Therefore, the results of many clinical trials are inconsistent with the results of mouse animal studies. Many clinical studies urgently need better animal models. Establishing humanized animal models is a very important development direction to overcome the shortcomings of traditional experimental animals. Animals produced by replacing or replacing endogenous cells or genes of animals with human cells or genes are called humanized animals to establish biological systems or disease models close to humans. Humanized animal models can be divided into gene humanization and cell (tissue) humanization.

　　By using mouse genetic engineering technology to replace human normal or mutant genes with mouse-like genes, and using immunodeficient mice (such as NSG mice), mice that are close to human normal or mutant gene systems can be established. . Stem cell transplantation technology can establish humanized mouse models and establish the hematopoietic and immune systems of mice. The genetically humanized mouse itself not only has important application value, but also can improve and enhance the cell humanized mouse model through genetic humanization, which has a huge promoting effect in the field of biomedicine. Transplant human hematopoietic stem cells into mice with severe immunodeficiency. It can establish the hematopoietic system and immune system of mice, and has important application value. For example, NOG mice cultured in the Central Laboratory of Animal Research in Japan and NSG mice cultured in the Jackson Laboratory in the United States are currently the most widely used severe immunodeficiency mice. This type of mice lacks T cells, B cells and NK cells, so they can effectively receive xenotransplantation. Transplant human hematopoietic stem cells, liver stem cells and primary tumor tissue cells into NOG and NSG mice. Human stem cells proliferate and differentiate normally in mice, and tumor cells proliferate to form tumors. The tumor formed by primary tumor tissue is very close to the clinical nature of mice. This is of great value for evaluating new drugs and studying cancer stem cells. Artificial hematopoietic stem cells must be killed in advance to rebuild the immune system. After transplanting artificial hematopoietic stem cells into immunodeficient mice (such as NOG and NSG mice), human cells lasted for a short time in the mice, and the hematopoietic stem cells could not proliferate in the mice and develop into other immune cells. No response to bone marrow cells, cytotoxic T cells, NK cells and B cell immunoglobulin antibodies. To improve NOG and NSG mice, it is necessary to establish genetically humanized mice, transfer artificial hematopoietic immune cell growth factor genes into mice, and human cytokines that support the growth, development and differentiation of human stem cells.

　　Cell humanized mouse is a promising animal model for studying artificial blood and immunity. OG and NSG mice are currently the best hosts for human cell transplantation, and human cells are rarely or rarely rejected. Cell humanized mice can be used in immunology, autoimmunity, transplantation, infectious diseases and tumor research. It has very special value in the research field of certain viral infections (such as HIV).