Development of a Robust Humanized Mouse Model

There has been a great need to study human immune responses to pathogenic infections in a systematic and controlled manner. For this reason, tremendous efforts have been devoted to reconstitute severe combined immunodeficient (scid) mice, which lack their own T and B lymphocytes, with human immune cells. However, early approaches were unsuccessful because of poor implantation efficiency, or rapid disappearance of human T and B cells from recipient mice, or rapid development of hematopoietic malignancies in recipient mice. A breakthrough was reported recently by using scid mice that were also deficient in the common gamma (gc) chain. Although the existing humanized mouse model begins to allow investigations of human pathogen infections in a small animal model, the current system is not ideal. For example, the immune response in the humanize mice is poor. In addition, it is difficult to genetically modify hematopoietic stem cells prior to their transfer into mice. Obviously, this is necessary if one would like to test specific gene function in the immune responses to the pathogen of interest. We have established the humanized mouse model and made significant progress in expanding human hematopoietic stem cells in vitro and genetically modifying them with lentivirus. We aim to develop a robust humanized mouse model for studying human immune responses to infections and evaluating therapeutics for human diseases in the hematopoietic system.