Non-obese diabetic-recombination activating gene-1 (NOD-Rag1 null) interleukin (IL)-2 receptor common gamma chain (IL2r gamma null) null mice: a radioresistant model for human lymphohaematopoietic engraftment
Shultz, Leonard D.
Miller, David M.
King, Marie A.
Burzenski, Lisa M.
Lyons, Bonnie L.
Rossini, Aldo A.
Greiner, Dale L.
Student AuthorsDavid M. Miller
UMass Chan AffiliationsDepartment of Medicine, Division of Diabetes
Document TypeJournal Article
KeywordsAnimals; Bone Marrow; Cord Blood Stem Cell Transplantation; Disease Models, Animal; Graft Survival; Humans; Immunophenotyping; Interleukin Receptor Common gamma Subunit; Mice; Mice, Inbred NOD; Mice, SCID; Peripheral Blood Stem Cell Transplantation; Radiation Tolerance; Spleen; Thymus Gland; Transplantation, Heterologous
Medicine and Health Sciences
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AbstractImmunodeficient hosts engrafted with human lymphohaematopoietic cells hold great promise as a preclinical bridge for understanding human haematopoiesis and immunity. We now describe a new immunodeficient radioresistant non-obese diabetic mice (NOD) stock based on targeted mutations in the recombination activating gene-1 (Rag1(null)) and interleukin (IL)-2 receptor common gamma chain (IL2rgamma(null)), and compare its ability to support lymphohaematopoietic cell engraftment with that achieved in radiosensitive NOD.CB17-Prkdc(scid) (NOD-Prkdc(scid)) IL2rgamma(null) mice. We observed that immunodeficient NOD-Rag1(null) IL2rgamma(null) mice tolerated much higher levels of irradiation conditioning than did NOD-Prkdc(scid) IL2rgamma(null) mice. High levels of human cord blood stem cell engraftment were observed in both stocks of irradiation-conditioned adult mice, leading to multi-lineage haematopoietic cell populations and a complete repertoire of human immune cells, including human T cells. Human peripheral blood mononuclear cells also engrafted at high levels in unconditioned adult mice of each stock. These data document that Rag1(null) and scid stocks of immunodeficient NOD mice harbouring the IL2rgamma(null) mutation support similar levels of human lymphohaematopoietic cell engraftment. NOD-Rag1(null) IL2rgamma(null) mice will be an important new model for human lymphohaematopoietic cell engraftment studies that require radioresistant hosts.
Clin Exp Immunol. 2008 Nov;154(2):270-84. Epub 2008 Sep 8.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/33056