Mice with a human immune system (HIS)

Human immune system (HIS) mice are a subset of humanized mice that are generated by the xenoengraftment of human immune cells or tissues and/or their progenitors (hematopoietic stem cells [HSCs]) into immunodeficient mice. Typically, the severely immunodeficient mice strains used for HIS mouse model generation harbor IL2γgnull mutations combined with knockout of the Rag gene or SCID mutations on the NOD or BALB/c genetic backgrounds, namely as NSG, NOG, and BRG et al. These mouse models exhibit dramatic improvements in rates of human cell engraftment and in their ability to recapitulate the human immune system. Resultant HIS model mice are broadly characterized into three categories based on differences in the sources of human immune cells and the approaches used to establish a functional human immune system, with each exhibiting unique advantages and limitations: Hu-PBL mice, Hu-HSC mice, and Hu-BLT mice, illustrated in detail below.