NKG-MHC-dKO(H2-K1/H2-Ab1/H2-D1) Mouse
Product Name
NKG-MHC-dKO(H2-K1/H2-Ab1/H2-D1) Mouse
Product ID
C001705
Strain Name
NOD.Cg-PrkdcscidIl2rgem1cyaH2-K1em1cyaH2-Ab1em2cyaH2-D1em1cya/Cya
Backgroud
NKG
Status
When using this mouse strain in a publication, please cite “NKG-MHC-dKO(H2-K1/H2-Ab1/H2-D1) Mouse (Catalog C001705) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
H2-Ab1 & H2-D1 & H2-K1
Gene Alias
IAb, Ia2, Ia-2, Abeta, H-2Ab, H2-Ab, Rmcs1, I-Abeta, H-2D, H2-D, H2-K1, K-f, H-2K, H2-K, H2-D1, H-2K(d)
NCBI ID
Chromosome
Chr 17 (Mouse), Chr 17 (Mouse), Chr 17 (Mouse)
MGI ID
Datasheet
Strain Description
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, 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. PBMC transplantation into NKG mice has the advantages of high immune reconstitution efficiency and fast speed. 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.
The mouse MHC, termed the H-2 complex, is located on chromosome 17 and encodes a suite of molecules fundamental to antigen processing and T cell-mediated immunity. These are broadly categorized into class I (e.g., H2-K1 and H2-D1), expressed ubiquitously on nucleated cells and specialized in presenting endogenous antigens to CD8+ cytotoxic T cells, and class II (e.g., H2-Ab1), predominantly expressed by professional antigen-presenting cells (APCs) such as macrophages, B cells, and dendritic cells, responsible for presenting exogenous antigens to CD4+ helper T cells [1–2]. Previous studies have demonstrated that dual knockout (dKO) of mouse MHC class I and II molecules mitigates GvHD by abrogating xenogeneic antigen presentation, thereby enabling sustained human immune cell engraftment [3–5].
NKG-MHC-dKO(H2-K1/H2-Ab1/H2-D1) mice, generated through targeted deletion of key MHC class I (H2-K1, H2-D1) and class II (H2-Ab1) molecules, effectively circumvent the immunological mismatch that triggers graft-versus-host disease (GvHD). This strategic ablation substantially delays GvHD onset and supports extended in vivo observation of human immune system reconstitution following PBMC engraftment. The model provides a high-resolution platform for longitudinal interrogation of human immune cell functionality and cross-species immune dynamics within a mouse host.
Reference
Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. The major histocompatibility complex and its functions.
Shiina T, Blancher A, Inoko H, Kulski JK. Comparative genomics of the human, macaque and mouse major histocompatibility complex. Immunology. 2017 Feb;150(2):127-138.
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.
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.
Brehm MA, Kenney LL, Wiles MV, Low BE, Tisch RM, Burzenski L, Mueller C, Greiner DL, Shultz LD. Lack of acute xenogeneic graft- versus-host disease, but retention of T-cell function following engraftment of human peripheral blood mononuclear cells in NSG mice deficient in MHC class I and II expression. FASEB J. 2019 Mar;33(3):3137-3151.
Strain Strategy
The mouse H2-K1, H2-Ab1, and H2-D1 genes are all located on chromosome 17, arranged in a 5' to 3' orientation as H2-K1, H2-Ab1, and H2-D1, respectively. In this model, all three genes were knocked out using gene-editing technology.
Figure 1. Diagram of the gene editing strategy for the generation of NKG-MHC-dKO(H2-K1/H2-Ab1/H2-D1) mice.
Application Area
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.
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