title: Nonirradiated NOD,B6.SCID Il2rγ-/- Kit(W41/W41) (NBSGW) mice support multilineage engraftment of human hematopoietic cells.
abstract: In this study, we demonstrate a newly derived mouse model that supports engraftment of human hematopoietic stem cells (HSCs) in the absence of irradiation. We cross the NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ (NSG) strain with the C57BL/6J-Kit(W-41J)/J (C57BL/6.Kit(W41)) strain and engraft, without irradiation, the resulting NBSGW strain with human cord blood CD34+ cells. At 12-weeks postengraftment in NBSGW mice, we observe human cell chimerism in marrow (97% ± 0.4%), peripheral blood (61% ± 2%), and spleen (94% ± 2%) at levels observed with irradiation in NSG mice. We also detected a significant number of glycophorin-A-positive expressing cells in the developing NBSGW marrow. Further, the observed levels of human hematopoietic chimerism mimic those reported for both irradiated NSG and NSG-transgenic strains. This mouse model permits HSC engraftment while avoiding the complicating hematopoietic, gastrointestinal, and neurological side effects associated with irradiation and allows investigators without access to radiation to pursue engraftment studies with human HSCs.
authors.affiliation: Morgridge Institute for Research, Madison, WI 53715, USA.
authors.forename: Brian E
authors.initials: BE
authors.lastname: McIntosh
authors.affiliation: Department of Surgery, University of Wisconsin, Madison, WI 53715, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Brown
authors.affiliation: Morgridge Institute for Research, Madison, WI 53715, USA.
authors.forename: Bret M
authors.initials: BM
authors.lastname: Duffin
authors.affiliation: Morgridge Institute for Research, Madison, WI 53715, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Maufort
authors.affiliation: Morgridge Institute for Research, Madison, WI 53715, USA; Biotechnology Center, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Vereide
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA; Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53715, USA.
authors.forename: Igor I
authors.initials: II
authors.lastname: Slukvin
authors.affiliation: Morgridge Institute for Research, Madison, WI 53715, USA; Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA. Electronic address: jthomson@morgridgeinstitute.org.
authors.forename: James A
authors.initials: JA
authors.lastname: Thomson
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D005838:Genotype; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D016130:Immunophenotyping; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D013997:Time Factors; D018183:Transplantation Chimera
chemical_list: D053631:Interleukin Receptor Common gamma Subunit; D019009:Proto-Oncogene Proteins c-kit