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 and providing an effective model for studying the human immune system. However, due to the lack of cytokine necessary for human NK cell development in mice, there are also differences between humans and mice in the relevant regulatory factors. When reconstructing the human immune system in severely immunodeficient mice, the proportion of reconstructed NK cells is relatively low, which is not conducive to drug development targeting NK cells.

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 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.