Evidence for an interferon-inducible gene, Ifi202, in the susceptibility to systemic lupus

The Nba2 locus is a major genetic contribution to disease susceptibility in the (NZB X NZW)F-1 mouse model of systemic lupus. We generated C57BL/6 mice congenic for this NZB locus, and these mice produced antinuclear autoantibodies characteristic of lupus. F-1 offspring of congenic and NZW mice developed high autoantibody levels and severe lupus nephritis similar to (NZB X NZW)F1 mice. Expression profiling with oligonucleotide microarrays revealed only two differentially expressed genes, interferon-inducible genes Ifi202 and Ifi203, in congenic versus control mice, and both were within the Nba2 interval. Quantitative PCR localized increased Ifi202 expression to splenic B cells and non-T/non-B cells. These results, together with analyses of promoter region polymorphisms, strain distribution of expression, and effects on cell proliferation and apoptosis, implicate Ifi202 as a candidate gene for lupus.