title: Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice.
abstract: The scid mutation was backcrossed ten generations onto the NOD/Lt strain background, resulting in an immunodeficient stock (NOD/LtSz-scid/scid) with multiple defects in adaptive as well as nonadaptive immunologic function. NOD/LtSz-scid/scid mice lack functional lymphoid cells and show little or no serum Ig with age. Although NOD/(Lt-)+/+ mice develop T cell-mediated autoimmune, insulin-dependent diabetes mellitus, NOD/LtSz-scid/scid mice are both insulitis- and diabetes-free throughout life. However, because of a high incidence of thymic lymphomas, the mean lifespan of this congenic stock is only 8.5 mo under specific pathogen-free conditions. After i.v. injection of human CEM T-lymphoblastoid cells, splenic engraftment of these cells was fourfold greater in NOD/LtSz-scid/scid mice than in C.B17/Sz-scid/scid mice. Although C.B-17Sz-scid/scid mice exhibit robust NK cell activity, this activity is markedly reduced in both NOD/(Lt-)+/+ and NOD/LtSz-scid/scid mice. Presence of a functionally less mature macrophage population in NOD/LtSz-scid/scid vs C.B-17Sz-scid/scid mice is indicated by persistence in the former of the NOD/Lt strain-specific defect in LPS-stimulated IL-1 secretion by marrow-derived macrophages. Although C.B-17Sz-scid/scid and C57BL/6Sz-scid/scid mice have elevated serum hemolytic complement activity compared with their respective +/+ controls, both NOD/(LtSz-)+/+ and NOD/LtSz-scid/scid mice lack this activity. Age-dependent increases in serum Ig levels (> 1 micrograms/ml) were observed in only 2 of 30 NOD/LtSz-scid/scid mice vs 21 of 29 C.B-17/Sz-scid/scid animals. The multiple defects in innate and adaptive immunity unique to the NOD/LtSz-scid/scid mouse provide an excellent in vivo environment for reconstitution with human hematopoietic cells.
authors.affiliation: Jackson Laboratory, Bar Harbor, ME 04609.
authors.forename: L D
authors.initials: LD
authors.lastname: Shultz
authors.forename: P A
authors.initials: PA
authors.lastname: Schweitzer
authors.forename: S W
authors.initials: SW
authors.lastname: Christianson
authors.forename: B
authors.initials: B
authors.lastname: Gott
authors.forename: I B
authors.initials: IB
authors.lastname: Schweitzer
authors.forename: B
authors.initials: B
authors.lastname: Tennent
authors.forename: S
authors.initials: S
authors.lastname: McKenna
authors.forename: L
authors.initials: L
authors.lastname: Mobraaten
authors.forename: T V
authors.initials: TV
authors.lastname: Rajan
authors.forename: D L
authors.initials: DL
authors.lastname: Greiner
mesh_terms: D000361:Agammaglobulinemia / Q000235:genetics / Q000276:immunology; D000367:Age Factors; D000818:Animals; D003165:Complement System Proteins / Q000032:analysis; D003433:Crosses, Genetic; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology*; D016130:Immunophenotyping; D007375:Interleukin-1 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology; D008136:Longevity; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D008223:Lymphoma / Q000235:genetics / Q000821:virology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD / Q000235:genetics / Q000276:immunology*; D008817:Mice, Mutant Strains / Q000235:genetics / Q000276:immunology*; D016513:Mice, SCID / Q000235:genetics / Q000276:immunology*; D011070:Poly I-C / Q000494:pharmacology; D016511:Severe Combined Immunodeficiency / Q000235:genetics; D016038:Skin Transplantation / Q000276:immunology; D013601:T-Lymphocytes / Q000637:transplantation; D013953:Thymus Neoplasms / Q000235:genetics / Q000821:virology; D014183:Transplantation, Heterologous
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D003165:Complement System Proteins; D011070:Poly I-C