Highly Sensitive Model for Xenogenic GVHD Using Severe Immunodeficient NOG Mice

Background. Several animal models for xenogenic (xeno) graft versus host disease (GVHD) have been developed in immunodeficient mice, such as C.B-17-scid and nonobese diabetes (NOD)/severe combined immunodeficiency (SCID), by human peripheral blood mononuclear cell (hPBMC) transplantation. However, these models pose problems because they require sublethal total body irradiation of the mice and a large number of hPBMCs to induce GVHD, and the timing of onset of GVHD is also unstable. The aim of this study is to establish improved murine models of xeno-GVHD using novel immunodeficient NOD/Shi-scid IL2r gamma(null) (NOG) mice. Methods. In three strains of immunodeficient mice, NOG, BALB/cA-RAG2(null) IL2r gamma(null), and NOD/SCID mice, GVHD was induced by transplantation of hPbMCs with or without total body irradiation, and the GVHD symptoms in these strains were compared. Results. After intravenous transplantation of hPBMCs, NOG mice showed early onset of GVHD symptoms and a small number of hPBMCs (2.5 x 10(6)) was sufficient to induce GVHD when compared with BALB/cA-RAG2(null) IL2r gamma(null) and NOD/SCID mice. In addition, total body irradiation was not always necessary in the present model. Conclusions. These results indicate that our model using the NOG mouse is a useful tool to investigate GVHD and to develop effective drugs for GVHD.