Figure 1.

The history of the development on immunodeficient mice for humanized mice model. In retrospect, nude mice or SCID mice were the first immunodeficient strains. Subsequently, their congenic strains were generated to improve engraftment capacities. NOD/SCID mice established in 1995 have been a milestone in this field, because of the severer phenotype than nude and SCID mice. In early 2000s, NOG, NSG and BRG mice were established by introducing the IL-2Rγ^null allele into NOD/SCID or BALB/cA RAG2^null mice. Due to the complete loss of murine immune systems, human hematopoiesis has been enormously enhanced in these mice. Currently, these strains were further improved by introducing human genes for various cytokines or HLA class I and II, so as to recapitulate a human bona fide hematopoiesis and immune system. The superscripts represent the respective references. BRG, BALB/cA-Rag2^nullIl2rγ^null; HLA, histocompatibility leukocyte antigen; NOD, nonobese diabetic; NSG, NOD/LtSz-Prkdc^scid Il2rg^tm1Wjl/J; SCID, severe combined immunodeficiency.