- Paper Report
- Open Access
An interferon-inducible gene in lupus susceptibility
- Floris van Gaalen1
© Biomed Central Ltd 2002
- Received: 22 January 2002
- Accepted: 25 January 2002
- Published: 29 January 2002
- inbred mice
Crossing New Zealand Black (NZB) and New Zealand White (NZW) mice generates one of the most studied animal models of human systemic lupus erythematosus (SLE). Genetic analyses have revealed that this model shares with human lupus a complex genetic basis. One locus that is consistently linked with lupus traits is the distal chromosome 1 locus known as the Nba2 locus (New Zealand black autoimmunity 2). In this paper the Nba2 locus was investigated for the presence of susceptibility genes. Nonautoimmune C57BL/1 (B6) mice were made congenic for Nba2. Subsequently, the congenic mice were crossed with NZW mice. Spleen cells from the B6.Nba2 animals were used to screen for candidate genes using oligonucleotide microarrays.
The B6.Nba2 congenic mice developed high levels of autoantibodies but only a small number developed lupus nephritis. However, offspring of the B6.Nba2 congenic mice crossed with NZW mice developed high levels of antibodies and severe lupus nephritis similar to NZB x NZW mice. Expression profiling of spleen cells of the B6.Nba2 mice showed only two differentially expressed genes, interferon-inducible genes Ifi202 and Ifi203. In B6.Nba2 mice, Ifi202 levels were higher whereas Ifi203 levels were lower than in controls. More importantly, both genes are located in the Nba2 interval. Quantitative PCR showed that Ifi202 transcripts are specifically increased in B cells and non T/non B cells of B6.Nba2 spleen cells.
Mouse models - generation of congenic strains, microroarray, PCR
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