Experiment
Previously identified lupus susceptibility QTLs Lmb1-Lmb4 were further studied using subcongenic line analysis. Reciprocal congenics were derived from parental strains MRL-Faslpr (lupus susceptible) and C57BL/6-Faslpr (lupus resistant).
Lmb1 maps to57.5 cM on mouse Chromosome 4. B6.MRL-Lmb1 Faslpr congenic animals displayed increased lymph node weight while MRL.B6-Lmb1 Faslpr reciprocal congenic animals displayed increased spleen weight and increased CD8+ and CD4-CD8- T cell percentages.
Lmb2 maps to 41 cM on mouse Chromosome 5. B6.MRL-Lmb2 Faslpr congenics displayed reduced CD4-CD8- splenic T cell percentages compared to background strain C57BL/6-Faslpr.
The Lmb3 locus at 28 cM on mouse chromosome 7 displayed a major effect on lupus susceptibility. B6.MRL-Lmb3 Faslpr congenic animals displayed significantly larger spleens and lymph nodes compared to background strain C57BL/6-Faslpr. Conversely, reciprocal congenic MRL.B6-Lmb3 Faslpr displayed smaller spleens and lymph nodes, reducedimmune complex glomerulonephritis, and reduced IgG autoantibodies compared to B6.MRL-Lmb3 Faslpr. Thus, it appears Lmb3 has a significant effect on promoting spontaneous autoimmunity. Generation of subcongenic lines localized Lmb3 to an interval between D7Mit350 (41 cM, 84 Mb) and D7Mit109 (66 cM, 136 Mb). Aem2, an antibody modifier QTL at 37 cM, maps near Lmb3. Myci1,a myocardial infarction QTL, maps to 69 cM.
Lmb4 maps to 41 cM on mouse Chromosome 10. The B6.MRL-Lmb4 Faslpr congenic displayed slightly larger lymph nodes compared to background strain C57BL/6-Faslpr.