Severe defect of NK cell function, impaired DC function VDJ recombination defect, no MHC-I and various NOD anomaliesĬombined effect of SCID and γc null on NOD background Impaired complement, macrophage and NK cell function VDJ recombination defect added to various NOD anomalies To avoid confusion, humanized mice are specifically defined in this review as mice with a human immune system reconstituted by engrafting human haematopoietic or mature immune cells and/or immune tissues.ĭNA-repair and VDJ recombination defect due to deficiency of DNA-PKĬombined effect of SCID and beige mutations Generally, mice constituted with human cells, tissues, organs or even human genes may all be considered as humanized mice, including models grafted with foetal human lung, kidney, pancreas, stomach, liver, ovarian, endometrium, nervous and skin tissues. In the present review, we will concentrate on the selection and pre-treatment of genetically modified SCID or Rag null mouse recipients, strategies for implanting human HSCs, mature immune cells and/or tissues, as well as the applications of these models in biomedical research. On the other hand, to improve the engrafting efficiency of human immune cells and/or tissues, different conditional regimens and transplantation strategies have been intensively pursued, including the depletion of host innate immune cells as well as implanting mature human immune cells, foetal thymus, liver tissues, bone marrow and CD34 + haematopoietic stem cells (HSCs), respectively. Recently, more and more genetically modified SCID or Rag nul mice including SCID/beige, non-obese diabetic/severe combined immunodeficiency (NOD/SCID), NOD/SCID/p2M null and NOD/SCID/γc nul, Rag null, NOD/LtSz-Rag1 nullPfp null and Rag2 nullγc nul mice have been employed to further enhance the reconstitution efficiency of human immune cells in the periphery, due to their deficiency of innate immunity ( Table 1). Severe combined immunodeficiency (SCID) or recombination activating gene (Rag) null mice, lacking T and B cells, were originally used as recipients to re-build human immunity. Immunodeficient mice with constituted human immunity have been developed to overcome these constraints and are now important research tools for the in vivo study of human haematolymphopoiesis and immune responses. Animal models with humanized immune systems would significantly advance our understanding on human immunobiology and immune-related diseases such as autoimmune diseases, virus infections, as well as tumour and graft rejections. The study of human immunobiology in vivo is limited by technical and ethical constraints. The applications of the humanized mice to study the development and response of human immune cells, human autoimmune diseases, virus infections, transplantation biology and tumour biology are reviewed as well. Here, elements of an ideal humanized mouse model are highlighted including genetic and non-genetic modification of recipient mice, transplantation strategies and proposals to improve engraftments. These mouse models with constituted human immunity (defined as humanized mice in the present text) have been widely used to investigate the basic principles of human immunobiology as well as complex pathomechanisms and potential therapies of human diseases. Peripheral constitution of human immunity in SCID or Rag null mice has been achieved by transplantation of mature human immune cells, foetal human thymus, bone marrow, liver tissues, lymph nodes or a combination of these, although efficiency needs to be improved. To overcome this limitation, humanized mouse models are developed based on immunodeficient characteristics of severe combined immunodeficiency (SCID) or recombination activating gene (Rag) null mice, which can accept xenografts. Biomedical research in human beings is largely restricted to in vitro studies that lack complexity of a living organism.
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