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 mic e congenic for this NZB locus, and these mice produced antinuclear autoanti bodies characteristic of lupus. F-1 offspring of congenic and NZW mice deve loped high autoantibody levels and severe lupus nephritis similar to (NZB X NZW)F1 mice. Expression profiling with oligonucleotide microarrays reveale d only two differentially expressed genes, interferon-inducible genes Ifi20 2 and Ifi203, in congenic versus control mice, and both were within the Nba 2 interval. Quantitative PCR localized increased Ifi202 expression to splen ic B cells and non-T/non-B cells. These results, together with analyses of promoter region polymorphisms, strain distribution of expression, and effec ts on cell proliferation and apoptosis, implicate Ifi202 as a candidate gen e for lupus.