NKG-Kit*V831M Mouse
Product Name
NKG-Kit*V831M Mouse
Product ID
I001175
Strain Name
NOD.Cg-PrkdcscidIl2rgem1Kitem2(V831M)/Cya
Backgroud
NKG
Status
When using this mouse strain in a publication, please cite “NKG-Kit*V831M Mouse (Catalog I001175) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Alias
gc, p64, [g]c, CD132, gamma(c), W, Bs, Fdc, Ssm, SCO1, SCO5, SOW3, CD117, c-KIT, Tr-kit, Gsfsco1, Gsfsco5, Gsfsow3
Chromosome
Chr X, Chr 5
Datasheet
Strain Description
NKG mice are a type of severe immunodeficient mouse developed by Cyagen by knocking out the Il2rg gene in the NOD-Scid background strain. This strain lacks mature T, B, and NK immune cells, has reduced complement activity, and weak phagocytic activity of macrophages against human cells. Therefore, 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.
Significant physiological and immunological differences exist between humans and mice in immunological research, making direct extrapolation of murine data to humans challenging. However, by transplanting human PBMCs or HSCs into immunodeficient mice, human immune components can partially or fully replace the murine immune system, creating an in vivo model that facilitates the study of human immune functions. Typically, successful reconstitution of HSCs in severely immunodeficient mice requires myeloablative irradiation to deplete endogenous murine HSCs. This process creates a niche for human HSC engraftment while reducing the risk of host immune rejection. Nevertheless, myeloablative irradiation is associated with off-target damage to various tissues and organs, impacting the survival and functional integrity of engrafted cells [1-2]. Thus, genetic modification of murine HSC function to obviate the need for irradiation during HSC reconstitution represents a significant advancement in improving post-reconstitution survival and overall health of the mice.
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 [3-4]. The NKG-Kit*V831M mouse strain is generated by introducing the W41 mutation (V831M) into the KIT gene of the NKG mouse. Compared to standard NKG mice, these mice eliminate the need for irradiation during HSC reconstitution, thereby avoiding the deleterious effects of irradiation on the hematopoietic, gastrointestinal, and nervous systems. This feature renders NKG-Kit*V831M mice an invaluable tool for developing and evaluating tumor immunotherapies and conducting drug efficacy assessments.
Reference
Wittenborn TR, Fahlquist Hagert C, Ferapontov A, Fonager S, Jensen L, Winther G, Degn SE. Comparison of gamma and x-ray irradiation for myeloablation and establishment of normal and autoimmune syngeneic bone marrow chimeras. PLoS One. 2021 Mar 17;16(3):e0247501.
De La Rochere P, Guil-Luna S, Decaudin D, Azar G, Sidhu SS, Piaggio E. Humanized Mice for the Study of Immuno-Oncology. Trends Immunol. 2018 Sep;39(9):748-763.
McIntosh BE, Brown ME, Duffin BM, Maufort JP, Vereide DT, Slukvin II, Thomson JA. Nonirradiated NOD,B6.SCID Il2rγ-/- Kit(W41/W41) (NBSGW) mice support multilineage engraftment of human hematopoietic cells. Stem Cell Reports. 2015 Feb 10;4(2):171-80.
Cosgun KN, Rahmig S, Mende N, Reinke S, Hauber I, Schäfer C, Petzold A, Weisbach H, Heidkamp G, Purbojo A, Cesnjevar R, Platz A, Bornhäuser M, Schmitz M, Dudziak D, Hauber J, Kirberg J, Waskow C. Kit regulates HSC engraftment across the human-mouse species barrier. Cell Stem Cell. 2014 Aug 7;15(2):227-38.
Strain Strategy
The W41 mutation (V831M) was introduced into the KIT gene of NKG mice using precise gene-editing technology.
Figure 1. Diagram of the gene editing strategy for the generation of NKG-Kit*V831M mice.
Application Area
Construction of humanized mouse models for the immune system;
Studies on the human immune and hematopoietic systems;
Xenotransplantation of human cell lines (CDX) for drug screening and efficacy evaluation;
Xenotransplantation of patient-derived tumor tissues (PDX) for drug screening and efficacy evaluation;
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