Highly sensitive model for xenogenic GVHD using severe immunodeficient NOG mice

Transplantation. 2009 Jun 15;87(11):1654-8. doi: 10.1097/TP.0b013e3181a5cb07.


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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Flow Cytometry
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / pathology
  • Humans
  • Immunohistochemistry
  • Interleukin Receptor Common gamma Subunit / deficiency
  • Kidney / pathology
  • Leukocytes, Mononuclear / transplantation*
  • Liver / pathology
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Transplantation, Heterologous / immunology*
  • Whole-Body Irradiation


  • Interleukin Receptor Common gamma Subunit