DESCRIPTION:

QTL associated with Y-linked autoimmune acceleration QTL 1. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (56424004)

LABEL:

QTL-Yaa1-Mouse-Chr 13

SCORE TYPE:

Binary

DATE ADDED:

2012-04-02

DATE UPDATED:

2024-04-25

SPECIES:

URI:

http://www.informatics.jax.org/searches/accession_report.cgi?id=MGI:1345663

AUTHORS:

Laporte C, Ballester B, Mary C, Izui S, Reininger L

TITLE:

The Sgp3 locus on mouse chromosome 13 regulates nephritogenic gp70 autoantigen expression and predisposes to autoimmunity.

JOURNAL:

Journal of immunology (Baltimore, Md. : 1950) Oct 2003, Vol 171, pp. 3872-7

ABSTRACT:

By interval mapping of a backcross progeny between New Zealand White (NZW) and C57BL/6 (B6) mice bearing the Y chromosome-linked autoimmune acceleration gene Yaa, we previously identified a genetic locus on mid-chromosome 13, here designated as Sgp3, showing a major effect on the expression of a nephritogenic autoantigen, gp70. In this study, the NZW-derived Sgp3 region was transferred by backcross procedure and marker-assisted selection on the B6 background to produce three independent congenic strains B6.NZW-Sgp3/1, -Sgp3/2, and -Sgp3/3. We show that NZW homozygosity at a single 3 centiMorgans ( approximately 12 megabases (Mb)) interval between markers D13Mit142 and D13Mit254 mediates increased basal serum levels of gp70 in B6.NZW-Sgp3/1 and B6.NZW-Sgp3/2 mice and with a higher degree in males ( approximately 15 micro g/ml) than in females ( approximately 9 micro g/ml) as compared with B6 ( approximately 2 micro g/ml), revealing a gender effect. However, their gp70 levels are still lower than that of NZW mice ( approximately 60 micro g/ml). In addition, B6.NZW-Sgp3/1 and B6.NZW-Sgp3/2 mice showed a moderate 2- to 3-fold increase in serum gp70 in response to LPS, which contrasted with over a 10-fold increase in NZW mice. Although both B6.NZW-Sgp3/1 and B6.NZW-Sgp3/2 mice failed to produce significant amounts of gp70 anti-gp70 immune complexes, unexpectedly, aged B6.NZW-Sgp3/2 congenic males bearing the Yaa gene developed increased titers of IgG autoantibodies to DNA and chromatin. Our data indicate that Sgp3 is involved in a complex process of gp70 production under polygenic control and may provide a significant contribution to lupus susceptibility not only through up-regulation of gp70 autoantigen production but also predisposition to autoimmunity. PUBMED: 14500689
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