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

Highly sensitive model for xenogenic GVHD using severe immunodeficient NOG mice.

Author information

1
Department of Laboratory Animal Research, Central Institute for Experimental Animals, Miyamae, Kawasaki, Japan. rito@ciea.or.jp

Abstract

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.

PMID:
19502956
DOI:
10.1097/TP.0b013e3181a5cb07
[Indexed for MEDLINE]

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