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Citations
IMMUNITY 47:107 (2017) IF=22.845
huHSC-NKG-hIL15 Mice
Catalog Number：C001526
Strain Name：huCD34+HSC-NOD.Cg-PrkdcscidIl2rgem1Il15em1(hIL15)/Cya
Genetic Background：NKG
Strain Description
NKG mice (Catalog Number: C001316) 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-15 (IL-15) is a cytokine that regulates the activation and proliferation of T cells and natural killer (NK) cells. It also plays a role in balancing the number of CD8+ memory cells alongside IL-2. Research indicates that IL-15 is essential for the differentiation, function, and survival of NK cells. Providing sufficient human IL-15 can help stabilize the function of human NK cells within a mouse model [1-2]. The NKG-hIL15 mice (Catalog Number: C001513) are constructed by knocking in the human IL15 gene from the NKG mice. Compared to NKG mice, NKG-hIL15 mice significantly enhance the reconstitution proportion of human NK cells after HSC or PBMC transplantation. These mice can be utilized for the development of immunotherapies targeting NK cells and drug evaluation.
The huHSC-NKG-hIL15 mouse refers to an immune system humanized mouse model constructed by transplanting human hematopoietic stem cells (HSC) into NKG-hIL15 mice after sub-lethal dose irradiation. This model can reconstitute various immune cells, has a long lifespan, and is particularly effective in rebuilding human NK cells, which can aid in the development of NK cell-related tumor immunotherapies.
Typically, 4 to 5-week-old female NKG-hIL15 mice are selected and after irradiation, they receive a tail vein injection of human CD34+ hematopoietic stem cells (HSC).
● Research on the human immune system, haematopoietic system;
● Human-derived cell line xenograft (CDX) and patient-derived xenograft (PDX);
● NK cell development mechanism studies, NK cell-related tumor immunotherapy development, and antibody-dependent NK cell-mediated toxicity (ADCC) studies.
1. Expression of the human IL15 protein
Figure 1. ELISA analysis of the human IL15 protein in the 5-week-old female homozygous NKG-hIL15 mice and NKG mice. Compared to NKG mice, NKG-hIL15 mice exhibit significant expression of the human IL15 protein.
2. huHSC-NKG-hIL15 mice for human immune system reconstitution
a. Survival and growth curves
Figure 2. Survival status of 4-week-old female huHSC-NKG-hIL15 mice. After myeloablation by irradiation, NKG-hIL15 mice were transplanted with 0.05M human CD34+ hematopoietic stem cells (huHSC) via tail vein injection to construct the huHSC-NKG-hIL15 model. The results demonstrate that huHSC-NKG-hIL15 mice can maintain normal growth, with body weight gradually increasing. These mice maintain a survival rate of approximately 78% at 225 days post engraftment.
b. Proportion of human leukocytes reconstructed
Figure 3. Variation of the human CD45+ leukocytes in the peripheral blood of huHSC-NKG-hIL15 mice. The results indicate that human leukocytes in the peripheral blood of huHSC-NKG-hIL15 mice rapidly reconstitute by the 3rd-week post engraftment*.
*The actual efficacy of human immune system reconstitution may vary based on donors and experimental conditions.
c. Human T and B cell reconstitution
Figure 4. Reconstruction effects of human T cells and B cells in huHSC-NKG-hIL15 mice. The results indicate that human T cells in huHSC-NKG-hIL15 mice begin to reconstitute by the 11th week and gradually increase in proportion. By the 27th week, the proportion of human T cells remains around 25%. Human B cells, on the other hand, fluctuate and gradually stabilize after the 3rd week, reaching stability around the 17th week.
d. Reconstitution of human NK cells
Figure 5. Reconstruction effects of human NK cells in huHSC-NKG-hIL15. The results indicate that human NK cells rapidly reconstitute between the 3rd and 5th weeks, followed by a subsequent decline in proportion. From the 13th week onward, there is a fluctuating increase, gradually stabilizing by the 17th week. Even at the 27th week, approximately 20% of NK cells can be maintained. Additionally, during the reconstruction process, NKG-hIL15 mice harbor NK cells at different developmental stages*. Notably, successful reconstruction of mature NK cells (CD57+) has been achieved.
*NKG2D: expressed during early NK cell development and remains active in mature NK cells; KIR3DL: expressed during mid-to-late NK cell development; CD57: expressed during the final stage of NK cell maturation.
References
[1] Katano I, Nishime C, Ito R, Kamisako T, Mizusawa T, Ka Y, Ogura T, Suemizu H, Kawakami Y, Ito M, Takahashi T. Long-term maintenance of peripheral blood derived human NK cells in a novel human IL-15- transgenic NOG mouse. Sci Rep. 2017 Dec 8;7(1):17230.
[2] Huntington ND, Legrand N, Alves NL, Jaron B, Weijer K, Plet A, Corcuff E, Mortier E, Jacques Y, Spits H, Di Santo JP. IL-15 trans-presentation promotes human NK cell development and differentiation in vivo. J Exp Med. 2009 Jan 16;206(1):25-34.
