title: Generation of Immunodeficient Mice Bearing Human Immune Systems by the Engraftment of Hematopoietic Stem Cells.
abstract: Immunodeficient mice are being used as recipients of human hematopoietic stem cells (HSC) for in vivo analyses of human immune system development and function. The development of several stocks of immunodeficient Prkdc (scid) (scid), or recombination activating 1 or 2 gene (Rag1 or Rag2) knockout mice bearing a targeted mutation in the gene encoding the IL2 receptor gamma chain (IL2rγ), has greatly facilitated the engraftment of human HSC and enhanced the development of functional human immune systems. These "humanized" mice are being used to study human hematopoiesis, human-specific immune therapies, human-specific pathogens, and human immune system homeostasis and function. The establishment of these model systems is technically challenging, and levels of human immune system development reported in the literature are variable between laboratories. The use of standard protocols for optimal engraftment of HSC and for monitoring the development of the human immune systems would enable more direct comparisons between humanized mice generated in different laboratories. Here we describe a standard protocol for the engraftment of human HSC into 21-day-old NOD-scid IL2rγ (NSG) mice using an intravenous injection approach. The multiparameter flow cytometry used to monitor human immune system development and the kinetics of development are described.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
authors.forename: Suheyla
authors.initials: S
authors.lastname: Hasgur
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
authors.forename: Ken Edwin
authors.initials: KE
authors.lastname: Aryee
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, 04609, USA.
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Shultz
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
authors.forename: Dale L
authors.initials: DL
authors.lastname: Greiner
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA. michael.brehm@umassmed.edu.|Program in Molecular Medicine, The University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA. michael.brehm@umassmed.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Brehm
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007275:Injections, Intravenous; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009154:Mutation
chemical_list: C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit
keywords: HSC; Hematopoietic stem cells; Humanized mice; IL2rγ; NSG; SCID; Thymus; Transplantation