Transgenic mice that are currently used to generate fully human antibodies cannot capture the complete human antibody repertoire, thus limiting the diversity of antibodies that can be produced. This study engineered the full complement of variable region genes from human immunoglobulin loci into precise locations in the mouse genome. Antigen immunization of these mice produced high-affinity mouse–human chimeric antibodies with broad epitope coverage and long human-like complementarity-determining region 3 (which binds antigens). The authors note that these mice could be used as models of the human antibody response, to discover therapeutic human monoclonal antibodies and to aid vaccine design.