title: Generation of hematopoietic humanized mice in the newborn BALB/c-Rag2null Il2rγnull mouse model: a multivariable optimization approach.
abstract: Hematopoietic humanized mice generated via transplantation of human hematopoietic stem cells (hHSCs) into immunodeficient mice are a valuable tool for studying development and function of the human immune system. This study was performed to generate a protocol that improves development and quality of humanized mice in the BALB/c-Rag2(null)Il2rγ(null) strain, testing route of injection, in vitro culture and freezing of hHSCs, types of cytokines in the culture, and co-injection of lineage-depleted CD34(-) cells. Specific hHSC culturing conditions and the addition of support cells were found to increase the frequency, and human hematopoietic chimerism, of humanized mice. The optimized protocol resulted in BALB/c-Rag2(null)Il2rγ(null) humanized mice displaying more consistent human hematopoietic and lymphoid engraftment. Thus, hematopoietic humanized mice generated on a BALB/c immunodeficient background represent a useful model to study the human immune system.
authors.affiliation: Integrated Department of Immunology, National Jewish Health and University of Colorado Denver School of Medicine, Denver, CO 80206, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Lang
authors.forename: Nicholas
authors.initials: N
authors.lastname: Weiss
authors.forename: Brian M
authors.initials: BM
authors.lastname: Freed
authors.forename: Raul M
authors.initials: RM
authors.lastname: Torres
authors.forename: Roberta
authors.initials: R
authors.lastname: Pelanda
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002469:Cell Separation; D004268:DNA-Binding Proteins / Q000172:deficiency*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007107:Immune System / Q000276:immunology*; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D023421:Models, Animal; D018183:Transplantation Chimera / Q000276:immunology*
chemical_list: D004268:DNA-Binding Proteins; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; C499308:Rag2 protein, mouse