Abstract

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)F(1) 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.