Polygenic control of susceptibility to murine systemic lupus erythematosus

Morel, Laurence; Rudofsky, Ulrich H.; Longmate, Jeffrey; Schiffenbauer, Joel; Wakeland, Edward K.

doi:10.1016/1074-7613(94)90100-7

Cited by 447 publications

(453 citation statements)

References 21 publications

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“…In this study, we confirm that there is a 129-derived locus on proximal chromosome 7 linked to GN. 6 Furthermore, this locus colocalizes with a number of loci from various lupusprone mouse strains, including Sle3 (NZM2401 locus linked to GN and ANA); 20,22 Lbw5 (NZW locus linked to mortality), 23 Lmb3 (MRL locus linked to splenomegaly, lymphadenopathy, anti-dsDNA Abs), 24 Nba3 (NZB locus linked to GN) 25 and Nba5. 26 As this is an analogous situation to that on distal chromosome 1, a similar haplotype-based candidate gene identification strategy could be applied, especially as murine single nucleotide polymorphism (SNP) databases continue to increase in both SNP density and the number of typed strains.…”

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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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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“…This locus has been defined for initial spontaneous loss of immunologic tolerance because of its variety of associated traits and may implicate multiple coexisting mechanisms. [46][47][48][49][50][51] There are several immediately interesting candidates within the region. Among these is a downstream effector molecule of an established type I interferon pathway, RnaseL.…”

Section: Genetic Control Of Viral Myocarditis In Micementioning

confidence: 99%

Complex genetic control of host susceptibility to coxsackievirus B3-induced myocarditis

et al. 2007

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The pathogenesis of viral myocarditis is a multifactorial process involving host genetics, viral genetics and the environment in which they interact. We have used a model of infection with coxsackievirus B3 (CVB3) to characterize the contribution of host genetics to viral myocarditis in mice of different genetic backgrounds but with a common H2 haplotype: A/J and B10.A-H2 a .Here we have used Evans blue dye as a quantitative biomarker for susceptibility to CVB3-induced myocarditis in addition to histopathological semiquantitative measures. We have found evidence of linkage between susceptibility to viral myocarditis and three loci. A locus on chromosome 1 centered on D1Mit200 was linked to sarcolemmal disruption in males (P ¼ 0.00005), a second locus on chromosome 4 centered on D4Mit81 was also linked to sarcolemmal disruption in males (P ¼ 0.0022). A third locus on distal chromosome 3 centered on D3Mit19 was linked to myocardial infiltration, with a logarithm of odds (LOD) score of 4.7 (P ¼ 0.0045), as well as sarcolemmal disruption in females (P ¼ 0.0015). These results provide strong evidence for the presence of loci contributing to the susceptibility of mice to viral myocarditis.

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“…1,2 Due to the complexity of genetic factors contributing to the pathogenesis of lupus, congenic dissection of lupus-prone mouse strains has been utilized to determine the immunologic mechanisms leading to its development. [3][4][5][6][7][8][9][10][11][12][13][14][15] Genetic linkage analysis of a lupus-prone strain, NZM2410, has indicated that development of lupus is a multistep process. 2 Three major non-major histocompatibility complex genomic intervals, Sle1 (on chromosome 1), Sle2 (on chromosome 4) and Sle3/5 (on chromosome 7, originally known as Sle3), were identified in this particular model.…”

Section: Introductionmentioning

confidence: 99%

“…2 Three major non-major histocompatibility complex genomic intervals, Sle1 (on chromosome 1), Sle2 (on chromosome 4) and Sle3/5 (on chromosome 7, originally known as Sle3), were identified in this particular model. 15 Functional analyses of congenic strains carrying Sle1, Sle2 or Sle3/5 have demonstrated that each interval is responsible for different component phenotypes. 5,6,8,12,14 Among them, the breach of immune tolerance to nuclear antigens mediated by Sle1 is essential for the initiation of lupus development.…”

Section: Introductionmentioning

confidence: 99%

“…The original B6-congenic strain that was produced contained both of these NZM2410-derived loci and is now termed as B6.Sle3/5. 12,15 It spans about a 45-cM region beginning at or near the centromere and terminating just distal to D7Mit40. Phenotypic characterization of the B6.Sle3/5 strain demonstrated that this interval mediates an elevated CD4/CD8 ratio with an increase in activated CD4 þ T cells, decreased susceptibility to activation-induced cell death and a break in humoral tolerance.…”

Section: Introductionmentioning

confidence: 99%

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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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Polygenic control of susceptibility to murine systemic lupus erythematosus

Cited by 447 publications

References 21 publications

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

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

Complex genetic control of host susceptibility to coxsackievirus B3-induced myocarditis

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

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