Aire deficiency causes lethal autoimmune disease in NOD mice, but only mild disease in C57BL/6 (B6) mice.
Most autoimmune diseases are caused by multiple genetic defects that conspire to break down the immune system's tolerance to self-tissues. One exception is autoimmunity caused by mutations in Aire, the transcriptional regulator that controls tolerance by driving the expression of tissue-restricted genes in thymic epithelial cells. Thymic expression of these genes causes self-reactive T cells to be either deleted or tolerized. Mice and humans with mutations in Aire develop autoimmune symptoms that vary widely in target organ and disease severity.In an attempt to explain this variation, Jiang and colleagues back-crossed Aire-deficient mice onto well-characterized mouse strains and showed that genetic...
