NKG-SGM3/hIL6/Kit*V831M Mouse

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.

Interleukin-6 (IL-6) is a cytokine that plays a crucial role in inflammation and B cell maturation. It is primarily produced and secreted into the bloodstream at acute and chronic inflammatory sites. IL-6 induces transcriptional inflammatory responses through its receptor, IL6Rα. Research indicates that immunodeficient mice carrying the human IL6 gene effectively enhance the differentiation of human monocytes and macrophages during HSC reconstruction ^[1].

The KIT gene encodes a receptor tyrosine kinase (c-Kit or CD117) that is activated by its ligand, stem cell factor (SCF). Activation of this receptor triggers phosphorylation of a variety of downstream intracellular proteins, governing essential cellular processes such as proliferation, differentiation, migration, and apoptosis across numerous cell types. The KIT gene plays a pivotal role in hematopoiesis, stem cell maintenance, gametogenesis, melanogenesis, and the development and function of mast cells. Mutations in KIT are implicated in a range of pathologies, including gastrointestinal stromal tumors, mastocytosis, and acute myeloid leukemia. Importantly, immunodeficient mice harboring the KIT W41 mutation (V831M) have demonstrated the ability to undergo human HSC transplantation without the need for irradiation, while maintaining high rates of engraftment ^[2-3].

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) ^[4], supporting stable engraftment of myeloid lineages and regulatory T cell populations ^[5].

NKG-SGM3/hIL6/Kit*V831M mice are mouse models obtained by mating KIT W41 mutation (V831M) mouse models (Catalog Number: I001175) with IL6 humanized mouse models (Catalog Number: I001176) and IL3, KITLG and CSF2 triple humanized mouse models (Catalog Number: I001177). These mice express human IL6, IL3, KITLG, and CSF2 genomic sequences, as well as mouse KIT genomic sequences carrying the W41 mutation (V831M). This model is a valuable tool for immuno-oncology, immunology, and infectious disease research.