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 × 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 deve...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2001-09, Vol.15 (3), p.435-443
Main Authors: Rozzo, Stephen J, Allard, John D, Choubey, Divaker, Vyse, Timothy J, Izui, Shozo, Peltz, Gary, Kotzin, Brian L
Format: Article
Language:English
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
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Summary: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.
ISSN:1074-7613
1097-4180
DOI:10.1016/S1074-7613(01)00196-0