1/12/2023 0 Comments Nod scid miceHowever, because no standardized system for evaluating immunodeficiency in mice currently exists, an objective comparison of the immunodeficiency of various immunodeficient mouse strains is difficult. Thus, a greater severity of immune deficiency led to a greater degree of tumor growth in immunodeficient mice.įollowing the development of large-scale mouse knockout programs and genome-editing tools, such as zinc-finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN) and the type II clustered, regularly interspaced, short palindromic repeat (CRISPR)-associated (Cas) system, it has become increasingly efficient to generate genetically modified mouse strains that cannot easily be generated using traditional hybridization. Consistently with immunodeficient patients, STAT-1−/− and RAG−/− mice showed a significantly increased incidence of observable cancers compared with their non-immunodeficient counterparts. For example, the occurrence of leukemia was higher in immunodeficient patients compared with the general population. Clinical data have demonstrated that immunodeficient individuals are susceptible to a dramatic increase in tumor incidence. Cancer cells and the host immune system constantly interact with one another in the tumor microenvironment. These mice withstood greatly increased engraftments of human tissues (hematopoietic stem cells (HSCs) and peripheral blood mononuclear cells (PBMCs)) than all previously developed immunodeficient humanized mouse models. A major breakthrough in the generation of humanized mice was the development of immunodeficient IL2Rg−/− mice, such as the NOD/ ShiLtSz-scid/IL2Rγ null (NSG) and NOD/ ShiJic-scid/IL2Rγ null (NOG) strains. The development of NOD.Cg- Prkdc scid (NOD- scid) mice with lower levels of NK cells and additional innate immune defects allowed higher levels of human cell engraftment, but the mice were still not ideal. The limitations that impeded human cell engraftment in scid and recombination-activating 2 deficient ( Rag2−/−) mice included the remaining mouse T and B cells and high levels of host NK cells. However, although nude mice lacked T cells, they harbored B cells and natural killer (NK) cells and did not allow lasting human cell reconstitution. The derivations of nude and severe combined immunodeficiency ( scid) mice, which are widely used for xenotransplantation, were milestones in the development of immunodeficient mice. Research on human diseases has relied on experiments using immunodeficient mouse models. The TEI score was effectively able to reflect the immunodeficiency of a mouse strain. We then validated that the NOD- scid-IL2Rg−/− (NSI) mice, which had the highest TEI score, were more suitable for xenograft and allograft experiments using multiple functional assays. Mice with a more severely impaired immune system attained a higher TEI score. In this study, we developed a tumor engraftment index (TEI) to quantify the immunodeficiency response to hematologic malignant cells and solid tumor cells of six immunodeficient mouse strains and C57BL/6 wild-type mouse (WT). However, due to the lack of a standardized system for evaluating the immuno-capacity that prevents tumor progression in mice, an objective choice of the appropriate immunodeficient mouse strains to be used for tumor engrafting experiments is difficult. Following the development of large-scale mouse knockout programs and genome-editing tools, it has become increasingly efficient to generate genetically modified mouse strains with immunodeficiency. The mouse is an organism that is widely used as a mammalian model for studying human physiology or disease, and the development of immunodeficient mice has provided a valuable tool for basic and applied human disease research.
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