Evidence for an Interferon-Inducible Gene, Ifi202, in the Susceptibility to Systemic Lupus

• Published in: Immunity (Cambridge, Mass.) Vol. 15; no. 3; pp. 435 - 443
• Main Authors: Rozzo, Stephen J, Allard, John D, Choubey, Divaker, Vyse, Timothy J, Izui, Shozo, Peltz, Gary, Kotzin, Brian L
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2001
• Subjects: Animals; Apoptosis; Carrier Proteins - genetics; Chromosome Mapping; Female; Genetic Predisposition to Disease; Ifi202 gene; interferon-inducible genes; Intracellular Signaling Peptides and Proteins; Lupus Erythematosus, Systemic - genetics; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred NZB; Oligonucleotide Array Sequence Analysis; oligonucleotides; Phosphoproteins - genetics; Polymorphism, Genetic; Promoter Regions, Genetic
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(01)00196-0

The
Nba2 locus is a major genetic contribution to disease susceptibility in the (NZB × 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 × 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.