The influence of Yaa on anti-DNA responses of B6-lpr mice

Pisetsky, David S.; Klatt, Cynthia; Dawson, Deborah V.; Roths, John B.

doi:10.1016/0090-1229(85)90106-0

Cited by 7 publications

(2 citation statements)

References 16 publications

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“… 53 The Yaa genetic locus was then bred onto other lupus-prone backgrounds and shown to accelerate and enhance disease expression. 55 56 This discovery was critical in demonstrating the important role of TLR7-inducing increased type I IFNs as a causative pathway for lupus. 53 Disease in the BXSB mouse is limited, similar to most other models, to glomerulonephritis.…”

Section: Introductionmentioning

confidence: 99%

Mouse models of lupus: what they tell us and what they don’t

2018

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Lupus is a complex heterogeneous disease characterised by autoantibody production and immune complex deposition followed by damage to target tissues. Animal models of human diseases are an invaluable tool for defining pathogenic mechanisms and testing of novel therapeutic agents. There are perhaps more applicable murine models of lupus than any other human disease. There are spontaneous models of lupus, inducible models of lupus, transgenic-induced lupus, gene knockout induced lupus and humanised mouse models of lupus. These mouse models of lupus have contributed significantly to our knowledge of the pathogenesis of lupus and served as valuable preclinical models for proof of concept for new therapies. Despite their utility, mouse models of lupus have their distinct limitations. Although similar, mouse and human immune systems are different and thus one cannot assume a mechanism for disease in one is translatable to the other. Efficacy and toxicity of compounds can vary significantly between humans and mice, also limiting direct translation. Finally, the heterogeneous aspects of human lupus, both in clinical presentation, underlying pathogenesis and genetics, are not completely represented in current mouse models. Thus, proving a therapy or mechanism of disease in one mouse model is similar to proving a mechanism/therapy in a limited subset of human lupus. These limitations, however, do not marginalise the importance of animal models nor the significant contributions they have made to our understanding of lupus.

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Section: Introductionmentioning

confidence: 99%

Mouse models of lupus: what they tell us and what they don’t

2018

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“…On autoimmune backgrounds such as MRL (5) or BXSB (9), the lpr mutation greatly accelerates lupus. In view of the abnormal peripheral deletion of autoreactive T and B cells resulting from these mutations and the autoantibodies produced spontaneously by B6/lpr and B6/ gld mice, lpr or gld would be expected to exacerbate autoantibody production in pristane-treated B6 mice.…”

Section: S Ystemic Lupus Erythematosus (Sle)mentioning

confidence: 99%

Fas and Fas Ligand Mutations Inhibit Autoantibody Production in Pristane-Induced Lupus

Satoh

Weintraub

Yoshida

et al. 2000

The Journal of Immunology

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Mutations of Fas (lpr) or Fas ligand (gld) cause a limited lupus-like syndrome in B6 mice by interfering with the deletion of autoreactive B and/or T cells. A more generalized lupus syndrome reminiscent of that of MRL mice can be induced in nonautoimmune strains by pristane, which causes a nonspecific inflammatory response in the peritoneal cavity. We hypothesized that, as in MRL mice, the lpr and gld mutations might accelerate lupus in pristane-treated mice. Pristane-treated B6 mice developed anti-nRNP/Sm, Su, and ribosomal P Abs, but little anti-ssDNA or chromatin. In contrast, B6/lpr and B6/gld mice spontaneously developed anti-ssDNA/chromatin Abs, but not anti-nRNP/Sm/Su/ribosomal P. Unexpectedly, B6/lpr and B6/gld mice were highly resistant to the induction by pristane of IgM anti-ssDNA (2 wk) and IgG anti-nRNP/Sm/Su/ribosomal P autoantibodies (6 mo), suggesting that intact Fas signaling is necessary. Interestingly, pristane did not enhance IgG chromatin Ab production in B6/lpr or B6/gld mice, suggesting that it did not influence the production of autoantibodies that develop spontaneously in the setting of Fas deficiency. Pristane treatment also decreased lymphoproliferation in B6/lpr mice. Increased production of IL-12 was associated consistently with the production of anti-nRNP/Sm/Su/ribosomal P as well as anti-DNA/chromatin. In contrast, production of anti-DNA/chromatin Abs was associated with IL-6 overproduction in pristane-treated mice, but not in lpr mice. The data strongly support the idea that different subsets of autoantibodies are regulated differentially by cytokine stimulation and/or Fas signaling.

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Autoimmunity: polyclonal activation or antigen induction?

Dziarski

1988

Immunology Today

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The influence of Yaa on anti-DNA responses of B6-lpr mice

Cited by 7 publications

References 16 publications

Mouse models of lupus: what they tell us and what they don’t

Mouse models of lupus: what they tell us and what they don’t

Fas and Fas Ligand Mutations Inhibit Autoantibody Production in Pristane-Induced Lupus

Autoimmunity: polyclonal activation or antigen induction?

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