NKG-SGM3 Mice

Catalog Number: I001177

Genetic Background: NKG

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 immunology research, direct studies on mice may not fully represent the human immune system due to physiological and immune system differences. However, by transplanting human peripheral blood mononuclear cells (PBMCs) or hematopoietic stem cells (HSCs) into immunodeficient mice, we can partially or completely replace the mouse immune system with a human counterpart. This approach enables in vivo simulation of human immune system function, providing an effective model for studying human immunity. In practical human-mouse xenotransplantation, using standard immunodeficient mice for transplantation may lead to differences in transplant efficiency due to the absence of specific human growth factors and supportive stromal cells within the mouse. Genetically modifying immunodeficient mice through gene editing techniques is a common strategy to enhance xenotransplantation efficiency.

The SCF gene, also known as KITLG, encodes the receptor-type protein-tyrosine kinase KIT ligand. This gene is crucial for the development of germ cells and neurons during embryogenesis and plays a significant role in hematopoiesis. The GM-CSF gene, or CSF2, encodes a cytokine that orchestrates the production, differentiation, and function of granulocytes and macrophages. Meanwhile, the IL3 gene encodes a growth-promoting cytokine essential for the proliferation of various blood cell types, influencing cell growth, differentiation, and apoptosis. Research demonstrates that severe immunodeficient mice expressing human IL3, GM-CSF (CSF2), and SCF (KITLG) show markedly enhanced engraftment efficiency in the xenotransplantation of acute myeloid leukemia (AML) ^[1], supporting stable engraftment of myeloid lineages and regulatory T cell populations ^[2]. NKG-SGM3 mice constructed by integrating human KITLG, CSF2, and IL3 genes into the genome of NKG mice can effectively enhance myeloid differentiation and improve the transplantation efficiency of hematopoietic and acute myeloid leukemia cells and thus are valuable for immuno-oncology, immunology, and infectious disease research.

Strain Strategy

Human SCF (KITLG), GM-CSF (CSF2), and IL3 genes were integrated into the genome of NKG mice using gene editing techniques.

Application

• Construction of an immune system humanized mouse model supporting stable engraftment of myeloid lineages and regulatory T cell populations;
• Research on the human immune system, hematopoietic systems, such as acute myeloid leukemia (AML);
• Human-derived cell line xenograft (CDX) and patient-derived xenograft (PDX).

Validation Data

1. Expression of the human IL3 and GM-CSF protein

Figure 1. ELISA analysis of the human IL3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) protein in heterozygous NKG-SGM3 mice and NKG mice. Compared to NKG mice, NKG-SGM3 mice exhibit significant expression of the human IL3 and GM-CSF protein.

References
[1]Wunderlich M, Chou FS, Link KA, Mizukawa B, Perry RL, Carroll M, Mulloy JC. AML xenograft efficiency is significantly improved in NOD/SCID-IL2RG mice constitutively expressing human SCF, GM-CSF and IL-3. Leukemia. 2010 Oct;24(10):1785-8.
[2]Billerbeck E, Barry WT, Mu K, Dorner M, Rice CM, Ploss A. Development of human CD4+FoxP3+ regulatory T cells in human stem cell factor-, granulocyte-macrophage colony-stimulating factor-, and interleukin-3-expressing NOD-SCID IL2Rγ(null) humanized mice. Blood. 2011 Mar 17;117(11):3076-86.