mt-Nd2a Modifies Resistance Against Autoimmune Type 1 Diabetes in NOD Mice at the Level of

OBJECTIVE—To investigate whether a single nucleotide poly-morphism (SNP) in the mitochondrial gene for NADH dehydro-genase 2 (mt-Nd2) can modulate susceptibility to type 1 diabetes in NOD mice. RESEARCH DESIGN AND METHODS—NOD/ShiLtJ mice conplastic for the alloxan resistant (ALR)/Lt-derived mt-Nd2a allele (NOD.mtALR) were created and compared with standard NOD (carrying the mt-Nd2c allele) for susceptibility to sponta-neous autoimmune diabetes, or to diabetes elicited by reciprocal adoptive splenic leukocyte transfers, as well as by adoptive transfer of diabetogenic T-cell clones. -Cell lines derived from either the NOD (NIT-1) or the NOD.mtALR (NIT-4) were also created to compare their susceptibility to cytolysis by diabeto-genic CD8 T-cells in vitro. RESULTS—NOD mice differing at this single SNP develope