Our lab uses a novel and long-lasting bone marrow, liver and thymus (BLT) humanized mouse model that is produced using the triple knock-out (TKO) C57BL/6 rag2-/-, common gamma chain-/-, CD47-/- mouse strain. This TKO-BLT mouse model has proven valuable for the study of the human immune response, pathogenesis and evaluation of therapeutics against HIV-1 and other viral diseases. TKO-BLT mice are highly reconstituted with human leukocytes and form secondary immune organs. The mice support sustained HIV-1 infection, mount HIV-1-specific immune responses, have a functional complement system and exhibit the hallmarks of a genuine human HIV-1 infection. Uniquely, these mice are resistant to graft versus host disease, which plagues other BLT models, and remain highly reconstituted and healthy for at least twice as long as other models. These qualities make TKO-BLT mice particularly amenable to the long-term investigations required to study pathogenesis in chronic infections and to trial therapeutic strategies over extended periods.
