title: Long-term human immune system reconstitution in non-obese diabetic (NOD)-Rag (-)-γ chain (-) (NRG) mice is similar but not identical to the original stem cell donor.
abstract: The murine immune system is not necessarily identical to it human counterpart, which has led to the construction of humanized mice. The current study analysed whether or not a human immune system contained within the non-obese diabetic (NOD)-Rag1(null) -γ chain(null) (NRG) mouse model was an accurate representation of the original stem cell donor and if multiple mice constructed from the same donor were similar to one another. To that end, lightly irradiated NRG mice were injected intrahepatically on day 1 of life with purified cord blood-derived CD34(+) stem and progenitor cells. Multiple mice were constructed from each cord blood donor. Mice were analysed quarterly for changes in the immune system, and followed for periods up to 12 months post-transplant. Mice from the same donor were compared directly with each other as well as with the original donor. Analyses were performed for immune reconstitution, including flow cytometry, T cell receptor (TCR) and B cell receptor (BCR) spectratyping. It was observed that NRG mice could be 'humanized' long-term using cord blood stem cells, and that animals constructed from the same cord blood donor were nearly identical to one another, but quite different from the original stem cell donor immune system.
authors.affiliation: Department of Immunobiology, University of Arizona, Tucson, AZ, USA.
authors.forename: D T
authors.initials: DT
authors.lastname: Harris
authors.forename: M
authors.initials: M
authors.lastname: Badowski
authors.forename: A
authors.initials: A
authors.lastname: Balamurugan
authors.forename: O O
authors.initials: OO
authors.lastname: Yang
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D036101:Cord Blood Stem Cell Transplantation; D005312:Fetal Blood / Q000166:cytology; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007107:Immune System / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013234:Stem Cells / Q000276:immunology*
chemical_list: D018952:Antigens, CD34; D018398:Homeodomain Proteins; D011948:Receptors, Antigen, T-Cell; C064658:RAG-1 protein
keywords: BCR; CD34; NRG mice; TCR; cord blood; spectratyping; stem cells
references.citation: Eur J Immunol. 2009 Aug;39(8):2136-45
references.pmid: 19572320
references.citation: J Immunol. 2010 Nov 15;185(10):5935-42
references.pmid: 20944001
references.citation: Clin Exp Immunol. 2008 Nov;154(2):270-84
references.pmid: 18785974
references.citation: Int Immunol. 2008 Jan;20(1):105-16
references.pmid: 18032374
references.citation: Int Immunol. 2009 Jul;21(7):843-58
references.pmid: 19515798
references.citation: Blood. 2010 Nov 18;116(20):4158-67
references.pmid: 20671122
references.citation: Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13022-7
references.pmid: 20615947
references.citation: Genes Immun. 2012 Jul;13(5):399-410
references.pmid: 22592523
references.citation: Science. 2004 Apr 2;304(5667):104-7
references.pmid: 15064419
references.citation: J Immunol. 2005 May 15;174(10):6477-89
references.pmid: 15879151
references.citation: Blood. 2010 Dec 16;116(25):5518-27
references.pmid: 20833978
references.citation: Bone Marrow Transplant. 1994 Feb;13(2):135-43
references.pmid: 8205082
references.citation: J Immunol. 2010 Sep 1;185(5):2710-20
references.pmid: 20668220
references.citation: Int Immunol. 1989;1(4):398-408
references.pmid: 2489036
references.citation: Clin Immunol. 2010 Apr;135(1):84-98
references.pmid: 20096637
references.citation: Nat Med. 2006 Nov;12(11):1316-22
references.pmid: 17057712
references.citation: Ann N Y Acad Sci. 2005 Jun;1044:236-43
references.pmid: 15958717