C-NKG B2m KO

 

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Product Number：C001416

Genetic Background：C-NKG

Reproduction：Homozygote x Homozygote


Strain Description

C-NKG mice are a type of severe immunodeficient mouse developed by Cyagen by deleting the Il2rg gene from the NOD-Scid strain. This strain lacks mature T, B, and NK cells, has reduced complement activity, and weak macrophage phagocytosis of human cells. As a result, C-NKG mice can efficiently engraft human hematopoietic stem cells (HSC), peripheral blood mononuclear cells (PBMC), patient-derived xenografts (PDX), or adult stem cells and tissues.

In the field of immunology research, there are differences between humans and mice in terms of physiology and immune systems, so research conducted directly on mice cannot fully reflect the human situation. By transplanting human peripheral blood mononuclear cells (PBMC) or human hematopoietic stem cells (HSC) into immunodeficient mice, the mouse’s immune system is partially or completely replaced by the human immune system, allowing for the simulation of human immune system function in vivo and providing an effective model for studying the human immune system. PBMC transplantation into C-NKG mice has the advantages of high immune reconstitution efficiency and fast speed. After 3 weeks of transplantation, the average proportion of human CD45+ cells in peripheral blood can reach about 50%. However, due to the mismatch between human immune cells and mouse MHC molecules, graft-versus-host disease (GvHD) occurs, where transplanted human immune cells (including T cells, B cells, and NK cells) attack mouse tissues, causing inflammation and tissue damage, ultimately leading to rapid death of the mouse. This results in a very limited experimental window.

The B2M gene encodes β2-microglobulin, a serum protein that exists on the surface of almost all nucleated cells in conjunction with the major histocompatibility complex (MHC) class I heavy chain. It is an essential component for the transport of MHC class I proteins to the cell surface. Studies have shown that knocking out the B2m gene in immunodeficient mice can lead to a lack of MHC class I molecule expression, thereby reducing graft-versus-host disease (GvHD) and extending the experimental window for PBMC immune reconstitution [1-2]. C-NKG B2m KO mice are constructed by knocking out the B2m gene on the background of C-NKG mice. Compared with C-NKG mice, C-NKG B2m KO mice have a significantly longer survival period after PBMC transplantation and can be used for long-term studies of PBMC immune system reconstitution.

 

Knockout of B2m gene in C-NKG mice by gene editing technology.

● Establishment of humanized immune system mouse model;

● Research on graft-versus-host disease (GvHD);

● Research on the immune system, hematopoietic system, and blood disease;

● Cell line-derived xenograft (CDX) and drug screening and efficacy evaluation;

● Patient-derived xenograft (PDX) and drug screening and efficacy evaluation.

1. Growth status of C-NKG B2m KO mice after PBMC transplantation

Figure 1. The survival and growth curves of C-NKG mice and C-NKG B2m KO mice after PBMC transplantation. Compared to C-NKG mice, C-NKG B2m KO mice have a higher survival rate, longer lifespan, and better growth status after transplantation.

 

2. GvHD occurrence in C-NKG B2m KO mice after PBMC transplantation in vivo

Figure 2. Comparison of GvHD scores after PBMC transplantation in C-NKG mice and C-NKG B2m KO mice. C-NKG B2m KO mice delayed the onset and reduced the severity of GvHD after transplantation and prolonged the experimental window compared to C-NKG mice.

 

3. Reconstitution of human-derived leukocytes after PBMC transplantation

Figure 3. Proportion of human CD45+ leukocytes in vivo after PBMC transplantation in C-NKG mice and C-NKG B2m KO mice. Consistent with C-NKG mice, C-NKG B2m KO mice can successfully rebuild the human immune system after PBMC transplantation.

 

4. Reconstitution of T cells after PBMC transplantation

Figure 4. Distribution of human T cells and subpopulations in vivo after PBMC transplantation in C-NKG mice and C-NKG B2m KO mice. After PBMC transplantation, the immune system reconstruction of both C-NKG mice and C-NKG B2m KO mice is mainly dominated by T cells. Four weeks after transplantation, the T cell subpopulations in C-NKG B2m KO mice are mainly CD4+ T cells.

References

[1]Yaguchi T, Kobayashi A, Inozume T, Morii K, Nagumo H, Nishio H, Iwata T, Ka Y, Katano I, Ito R, Ito M, Kawakami Y. Human PBMC-transferred murine MHC class I/II-deficient NOG mice enable long-term evaluation of human immune responses. Cell Mol Immunol. 2018 Nov;15(11):953-962.

[2]Cogels MM, Rouas R, Ghanem GE, Martinive P, Awada A, Van Gestel D, Krayem M. Humanized Mice as a Valuable Pre-Clinical Model for Cancer Immunotherapy Research. Front Oncol. 2021 Nov 18;11:784947.