NOR/Lt mice: MHC-matched diabetes-resistant control strain for NOD mice.
NOR/Lt is an insulitis-resistant and diabetes-free strain produced from an isolated genetic contamination within an NOD/Lt pedigree line. The albino coat-color phenotype, strain-specific endogenous retroviral profile, and skin graft tests indicated an NOD/Lt x C57BL/KsJ outcross-backcross segregant as the source of the contaminating genome. Analysis of 53 polymorphic DNA, biochemical, and immunologic markers distinguishing NOD/Lt from C57BL/KsJ revealed that 4 chromosomes (chromosomes 2, 4, 11, and 12) in NOR/Lt contained C57BL/KsJ-derived genes. The remaining markers on 14 chromosomes, including the diabetogenic H-2g7 complex on chromosome 17, were of NOD origin. Although completely resistant to cyclophosphamide-induced diabetes, NOR/Lt mice exhibited the same peripheral T-lymphocyte accumulation characteristic of NOD/Lt. Similarly, NOR/Lt peritoneal macrophages exhibited depressed interleukin-1 secretion characteristic of NOD/Lt. In addition to their diabetes resistance, NOR/Lt mice were distinguished from NOD/Lt by exhibiting more robust suppressor T-lymphocyte function. Outcross of NOR/Lt with NOD/Lt to generate heterozygosity at those chromosomal segments, defined by C57BL/KsJ markers in NOR/Lt parentals, did not produce insulitis or diabetes in F1 females. However, these F1 females were sensitive to cyclophosphamide-induced diabetes. In summary, the NOR/Lt strain is an MHC-matched diabetes-resistant control strain for NOD/Lt. Moreover, NOR/Lt will help identify the location and function of a non-MHC gene or genes capable of conferring resistance against insulitis and diabetes.
Prochazka
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Jackson Laboratory, Bar Harbor, Maine 04609.
Serreze
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Frankel
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Leiter
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D000818:Animals; D003433:Crosses, Genetic; D003520:Cyclophosphamide / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005819:Genetic Markers; D006650:Histocompatibility Testing; D007113:Immunity, Innate / Q000235:genetics; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D016688:Mice, Inbred NOD / Q000235:genetics*; D008815:Mice, Inbred Strains / Q000235:genetics*; D010182:Pancreatic Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016038:Skin Transplantation / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D005819:Genetic Markers; D003520:Cyclophosphamide