Current advances in humanized mouse models.
Humanized mouse models that have received human cells or tissue transplants are extremely useful in basic and applied human disease research. Highly immunodeficient mice, which do not reject xenografts and support cell and tissue differentiation and growth, are indispensable for generating additional appropriate models. Since the early 2000s, a series of immunodeficient mice appropriate for generating humanized mice has been successively developed by introducing the IL-2Rγ(null) gene (e.g., NOD/SCID/γc(null) and Rag2(null)γc(null) mice). These strains show not only a high rate of human cell engraftment, but also generate well-differentiated multilineage human hematopoietic cells after human hematopoietic stem cell (HSC) transplantation. These humanized mice facilitate the analysis of human hematology and immunology in vivo. However, human hematopoietic cells developed from HSCs are not always phenotypically and functionally identical to those in humans. More recently, a new series of immunodeficient mice compensates for these disadvantages. These mice were generated by genetically introducing human cytokine genes into NOD/SCID/γc(null) and Rag2(null)γc(null) mice. In this review, we describe the current knowledge of human hematopoietic cells developed in these mice. Various human disease mouse models using these humanized mice are summarized.
Central Institute for Experimental Animals, Kawasaki, Japan.
Ryoji
R
Ito
Takeshi
T
Takahashi
Ikumi
I
Katano
Mamoru
M
Ito
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007154:Immune System Diseases / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D014183:Transplantation, Heterologous
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C499308:Rag2 protein, mouse; C064658:RAG-1 protein