Humanized Mouse Model for HIV-1 Research

NOD Rag1^−/− IL2Rγ^NULL mice were humanized with hematopoietic stem cells (HSCs), as previously described (Klein et al., 2012 (link)). In brief, human fetal livers were procured from Advanced Bioscience Resources, Inc. and HSCs were isolated using a CD34⁺ isolation kit (Stem Cell Technologies, Inc.). Mice (NOD.Cg-Rag1^tm1Mom Il2rg^tm1Wjl/SzJ) were obtained from The Jackson Laboratory and bred and maintained at the Comparative Bioscience Center of The Rockefeller University. Between 1–5-d-old mice were irradiated with 100 cGy and injected with 2 × 10⁵ human HSCs. HSCs used to reconstitute the mice were obtained from human fetal liver tissues of 12 different donors. In the experiments shown, up to 12 humanized mice shared the same donor. Engraftment was evaluated by FACS analysis of the peripheral blood as previously described (Klein et al., 2012 (link)) and mice with successful reconstitution of human lymphocytes were challenged with HIV-1_YU2 or HIV-1_YU2^TM2. All experiments were performed under approval of the Institutional Review Board and the Institutional Animal Care and Use Committee of The Rockefeller University.