Association of Extensive Polymorphisms in the SLAM/CD2 Gene Cluster with Murine Lupus

Wandstrat, Amy E.; Nguyen, Charles; Limaye, Nisha; Chan, Alice; Subramanian, Srividya; Tian, Xiang Hong; Yim, Young Sun; Pertsemlidis, Alexander; Garner, Harold R.; Morel, Laurence; Wakeland, Edward K.

doi:10.1016/j.immuni.2004.10.009

Cited by 243 publications

(356 citation statements)

References 50 publications

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“…It has been demonstrated that expression of Sle1 is responsible for the increased survival of autoreactive B-cell clones. 26,27 Addition of Sle3 and Sle5 may further lower the threshold for B-cell activation and increase the tendency for autoreactive B cells to proliferate/differentiate upon stimulation by autoantigens. Therefore, the variability of antigen reactivity in different mice of the same strain may be in part due to the stochastic encounters of these B-cell clones with different autoantigens.…”

Section: Discussionmentioning

confidence: 99%

Sle3 and Sle5 can independently couple with Sle1 to mediate severe lupus nephritis

Liu

et al. 2007

Genes Immun

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Genetic analyses of the lupus-prone NZM2410 mouse have identified multiple susceptibility loci on chromosome 7, termed Sle3 and Sle5. Both of these loci were contained within a large congenic interval, originally termed as Sle3 that strongly impacts a variety of myeloid and T-cell phenotypes and mediates fatal lupus nephritis when combined with Sle1. We have now produced two subcongenic strains, B6.Sle3 and B6.Sle5, carrying the Sle3 and Sle5 intervals separately and characterized their phenotypes as monocongenic strains and individually in combination with Sle1. Neither B6.Sle3 nor B6.Sle5 monocongenic strain develop severe autoimmunity; however, both of these intervals cause the development of severe glomerulonephritis when combined with Sle1. Thus, B6.Sle1Sle3 and B6.Sle1Sle5 exhibit splenomegaly, expansion of activated B and CD4 þ T-cell populations and high levels of IgG and IgM autoantibodies targeting multiple nuclear antigens, intact glomeruli and various other autoantigens. In addition, B6.Sle1Sle3 mice also produced higher levels of IgA antinuclear autoantibodies, which were implicated in the development of IgA nephropathy. Our results indicate that Sle3 and Sle5 can independently complement with Sle1, through shared and unique mechanisms, to mediate the development of severe autoimmunity.

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Section: Discussionmentioning

confidence: 99%

Sle3 and Sle5 can independently couple with Sle1 to mediate severe lupus nephritis

Liu

et al. 2007

Genes Immun

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“…This is in agreement with our previous study, 6 in which SLE traits were mapped in (129 Â C57BL/6)F2 wild-type and (129 Â C57BL/6)F2.ApcsÀ/À mice. The linkages were markedly increased when we enlarged the sample size by combining data from the 21 The autoimmune-associated haplotype of the lupus-prone NZM2410 (NZW) strain, named the Slam/Cd2 haplotype 2, is also present in the 129/SvJ mice, 21 indicating that these two strains may share the same pathways leading to loss of peripheral tolerance when in combination with one or more polymorphic genes in the B6 genome. These observations give compelling evidence for the presence of a 129 locus influencing systemic autoimmunity on telomeric chromosome 1 as revealed in the context of B6 genome.…”

Section: Discussionmentioning

confidence: 99%

Identification of chromosome intervals from 129 and C57BL/6 mouse strains linked to the development of systemic lupus erythematosus

et al. 2006

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“…21 This may rule out Fcgr2b as the candidate monocytosis gene. However, Ifi202 is also overexpressed in Bxs2/3 mice 22 and the signalling lymphocyte activation molecule (SLAM) locus is the same haplotype as NZB 23 (unpublished NJ Rogers, SJ Rose and BJ Morley), all of which are strong candidates.…”

Section: Discussionmentioning

confidence: 99%

Monocytosis in BXSB mice is due to epistasis between Yaa and the telomeric region of Chromosome 1 but does not drive the disease process

et al. 2007

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The BXSB murine model of systemic lupus erythematosus is differentiated from other murine models of lupus by a severe monocytosis. The recently identified Y-linked autoimmune accelerator locus, Yaa, which is fundamental to accelerated disease in male BXSB mice, is required for the monocytic phenotype in BXSB. It has also recently been shown to induce monocytosis in combination with the Nba2 locus from NZB. To dissect the genetic basis and associated pathogenicity of BXSB-related monocytosis, a panel of existing congenic mice were studied and a novel sub-congenic mouse B10.Y BXSB .BXSB-Bxs3 was generated. Monocytosis was found to be caused by an epistatic interaction between Yaa and the telomeric region of chromosome 1, an area of approximately 30 cM. Bxs3 and Yaa together were sufficient to generate monocytosis equivalent to that of BXSB. In contrast to the NZB model, however, where monocytosis tightly correlated with autoantibody production and lethal lupus nephritis, this was not the case in BXSB. While Yaa þ mice bearing the Bxs3 locus drive monocytosis, glomerulonephritis and autoantibody production, both autoantibody production and nephritis are discreet events that occur in the absence of the Bxs3 locus. Yaa is a pre-requisite for monocytosis, demonstrating a novel synergistic interaction between Yaa and Bxs3.

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Association of Extensive Polymorphisms in the SLAM/CD2 Gene Cluster with Murine Lupus

Cited by 243 publications

References 50 publications

Sle3 and Sle5 can independently couple with Sle1 to mediate severe lupus nephritis

Sle3 and Sle5 can independently couple with Sle1 to mediate severe lupus nephritis

Identification of chromosome intervals from 129 and C57BL/6 mouse strains linked to the development of systemic lupus erythematosus

Monocytosis in BXSB mice is due to epistasis between Yaa and the telomeric region of Chromosome 1 but does not drive the disease process

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