Basic study to establish "humanized animal model" by improvement and modification of severely immunodeficient NOG mouse

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Severe immunodeficient NOG mice reported by us in 2002 show extremely high engraftment potential for xenogenic cells and tissues. Therefore, these mice enable us to generate "humanized mice" in which human cells and tissues act in the same way in humans by transplantation of human cells and tissues into NOG mice. The objective of this project is to improve immunodeficient mice including NOG mice by introducing human genes or by inactivating mouse genes to facilitate the generation of humanized mice. In the 4-year project period, we have newly established 33 strains of immunodeficient mice, and are working on 10 strains are in progress. By using NOG mice and these improved immunodeficient mice, we established various humanized models including those for infectious diseases, GVHD, cancer metastasis, human liver metabolism and stem cell differentiation. These models may be useful to evaluate new drug efficacy and safety, and also to analyze the mechanisms underlying human diseases.