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. PBMC transplantation into NKG mice has the advantages of high immune reconstitution efficiency and fast speed. After 3 weeks of transplantation, the average proportion of human CD45+ cells in peripheral blood can reach about 50%. However, due to the mismatch between human immune cells and mouse MHC molecules, graft-versus-host disease (GvHD) occurs, where transplanted human immune cells (including T cells, B cells, and NK cells) attack mouse tissues, causing inflammation and tissue damage, ultimately leading to rapid death of the mouse. This results in a very limited experimental window.

The B2M gene encodes β2-microglobulin, a serum protein that exists on the surface of almost all nucleated cells in conjunction with the major histocompatibility complex (MHC) class I heavy chain. It is an essential component for the transport of MHC class I proteins to the cell surface. Studies have shown that knocking out the B2m gene in immunodeficient mice can lead to a lack of MHC class I molecule expression, thereby reducing graft-versus-host disease (GvHD) and extending the experimental window for PBMC immune reconstitution ^[1-2]. NKG B2m KO mice are constructed by knocking out the B2m gene on the background of NKG mice. Compared with NKG mice, NKG B2m KO mice have a significantly longer survival period after PBMC transplantation and can be used for long-term studies of PBMC immune system reconstitution.