DESCRIPTION:

QTL associated with systemic lupus erythmatosus susceptibility 1. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (171141303)

LABEL:

QTL-Sle1-Mouse-Chr 1

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:105969

AUTHORS:

Peters AL, Stunz LL, Meyerholz DK, Mohan C, Bishop GA

TITLE:

Latent membrane protein 1, the EBV-encoded oncogenic mimic of CD40, accelerates autoimmunity in B6.Sle1 mice.

JOURNAL:

Journal of immunology (Baltimore, Md. : 1950) Oct 2010, Vol 185, pp. 4053-62

ABSTRACT:

EBV infection is associated with development of the autoimmune disease systemic lupus erythematosus (SLE), and EBV can reactivate during SLE flares. Latent membrane protein 1 (LMP1) is an EBV-encoded oncogenic mimic of CD40 that can be re-expressed in PBMCs during SLE flares, as >90% of humans are latently EBV-infected. Whether LMP1 signaling exacerbates SLE is unknown. The phenotype of mice expressing a chimeric molecule with the mouse CD40 extracellular domain and the LMP1 intracellular signaling regions (mCD40-LMP1 transgenic [tg]) includes enhanced autoreactivity, yet these mice do not develop fatal autoimmune disease. We hypothesized that LMP1-mediated activation signals cooperate with and/or amplify events that predispose individuals to development of autoimmunity. To determine which aspects of autoimmunity may be exacerbated by LMP1, we bred mCD40-LMP1tg mice to two lupus-prone strains, B6.Sle1 and B6.Sle3, and analyzed autoimmunity parameters. LMP1(+)Sle1(+/+) mice developed enlarged lymphoid organs containing increased frequencies of germinal center, B cells, CD86(+) B cells, and activated and memory T cells compared with non-tg littermates. Anti-histone Abs were elevated in serum of LMP1(+)Sle1(+/+) mice, and they had signs of kidney pathology. LMP1(+)Sle1(+/+) B cells produced increased IL-6 and upregulated CD86 to a higher degree following CD40 stimulation in vitro, suggesting that the in vivo autoimmune exacerbation is B cell intrinsic. In contrast, the LMP1 transgene has no additional effects on autoimmunity on the B6.Sle3 background. These data indicate that LMP1-induced effects can cooperate with distinct subsets of host genes that predispose to autoimmunity and can thus be an exacerbating factor in autoimmune disease via multiple mechanisms. PUBMED: 20810985
Find other GeneSets from this publication