Abstract: Described herein are transgenic mice for testing immunogenicity and protective efficacy of a wide variety of therapeutic agents and vaccines, determining allograft rejection, and developing monoclonal antibodies and generating hybridomas. Methods of generating a transgenic mouse is also described. Described herein are mouse models capable of expressing B cell, a T cell, a monocyte, a macrophage, a dendritic cell, a NK cell, a iNKT cell, an innate lymphoid cell, a microglia cell, a red blood cell, which can develop into a functional human immune system.