Faculty Research 1990 - 1999

Title

NOR/Lt mice: MHC-matched diabetes-resistant control strain for NOD mice.

Document Type

Article

Publication Date

1992

Keywords

Crosses-Genetic, Cyclophosphamide, Diabetes-Mellitus-Experimental: ge, im, pa, Genetic-Markers, Histocompatibility-Testing, Immunity-Natural: ge, Immunophenotyping, Lymphocyte-Transformation, Major-Histocompatibility-Complex, Mice, Mice-Inbred-C57BL: ge, Mice-Inbred-NOD: ge, Mice-Inbred-Strains: ge, Pancreatic-Diseases: ge, im, pa, Skin-Transplantation: im, Spleen: im, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, T-Lymphocytes: im

JAX Source

Diabetes 1992 Jan;41(1):98-106

Grant

DK36175, DK27722

Abstract

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.

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