Linkage analysis of systemic lupus erythematosus induced in diabetes-prone nonobese diabetic mice by Mycobacterium bovis

Systemic lupus erythematosus induced by Mycobacterium bovis in diabetes-prone nonobese diabetic mice was mapped in a backcross to the BALB/c strain. The subphenotypes-hemolytic anemia, antinuclear autoantibodies, and glomerular immune complex deposition-did not cosegregate, and linkage analysis for each trait was performed independently. Hemolytic anemia mapped to two loci: Bah1 at the MHC on chromosome 17 and Bah2 on distal chromosome 16, Antinuclear autoantibodies mapped to three loci: Banal at the MHC on chromosome 17, Bana2 on chromosome 10, and Bana3 on distal chromosome 1. Glomerular immune complex deposition did not show significant linkage to any genomic region, Mapping of autoantibodies (Coombs' or antinuclear autoantibodies) identified two loci: Babs1 at the MHC and Babs2 on distal chromosome 1, It has previously been reported that genes conferring susceptibility to different autoimmune diseases map nonrandomly to defined regions of the genome, One possible explanation for this clustering is that some alleles at loci within these regions confer susceptibility to multiple autoimmune diseases-the "common gene" hypothesis. With the exception of the H2, this study failed to provide direct support for the common gene hypothesis, because the loci identified as conferring susceptibility to systemic lupus erythematosus did not colocalize with those previously implicated in diabetes, However, three of the four regions identified had been previously implicated in other autoimmune diseases.