Alteration of DNA methylation levels in MRL lupus mice

Mizugaki, Michinao; Yamaguchi, Takahumi; Ishiwata, Shunji; Shindo, Hiroki; Hishinuma, Takanori; Nozaki, Seishiro; Nose, Masato

doi:10.1111/j.1365-2249.1997.tb08326.x

Cited by 32 publications

(29 citation statements)

References 24 publications

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“…However, hypomethylation is not observed in lymphocytes from SLE patients with overexpression of the c-myc gene [23]. In MRL/lpr mice, DNA methylation of genes in cells from the thymus and axillary lymph nodes decreases with ageing, while methylation of spleen cell genes increases with ageing and is related to the progression of disease activity, but there is no significant change of methylation with ageing in peripheral blood cells [24]. Administration of 5-aza C to MRL/lpr mice markedly prolongs their survival, decreases lymphadenopathy/splenomegaly and reduces circulating autoantibodies.…”

Section: Methylation Of Dna In Human and Mouse Slementioning

confidence: 91%

DNA methylation: its contribution to systemic lupus erythematosus

et al. 2006

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Recent studies on epigenetics, including the methylation of DNA and the enzymes regulating methylation, seem likely to contribute to understanding the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). In fact, the relationship between DNA methylation and SLE has long been the subject of investigation. To obtain a deeper understanding of the role of DNA methylation in the onset of SLE, we reviewed the findings reported in the literature and our own data about DNA methylation and SLE. Various studies have indicated the possible importance of DNA methylation, especially hypomethylation, in the aetiology of SLE. Epigenetic studies may provide clues for elucidating the pathogenesis of SLE and for developing new strategies to treat this disease.

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Section: Methylation Of Dna In Human and Mouse Slementioning

confidence: 91%

DNA methylation: its contribution to systemic lupus erythematosus

et al. 2006

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“…This mechanism might explain the particular susceptibility of the MRL strain to TCE effects on apoptosis and the induction of autoimmunity. Hypomethylation of DNA was shown to be increased in the thymus and lymph nodes of MRL +/+ mice when compared with Fas-deficient MRL-lpr/lpr mice (Mizugaki et al, 1997). In Fas-deficient MRL-lpr/lpr mice, increased and accelerated autoimmune diseases are linked to the lpr (lymphoproliferation) gene and this accounts for the higher sensitivity of the MRL +/+ strain to altered apoptosis.…”

Section: Figmentioning

confidence: 97%

Trichloroethylene Does Not Accelerate Autoimmune Diabetes in NOD Mice

Ravel¹,

Christ²,

Perron-Lepage³

et al. 2005

Journal of Immunotoxicology

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Pre-existing or contributing risk factors, including genetic predisposition and environmental influences, are largely thought to play a crucial (though ill-elucidated) role in the development of autoimmunity. Trichloroethylene (TCE) is a widely used organic solvent, which has been suspected of increasing the prevalence of autoimmune diseases, e.g., lupus, following environmental contamination. Although few epidemiological data are available, several studies reported an accelerated and more severe disease in TCEexposed autoimmunity-prone MRL +/+ mice. To test whether TCE can exert similar deleterious effects on organ-specific autoimmune diseases, non obese diabetic (NOD) mice were given 5 mg/ml TCE via the drinking water for 12 weeks. TCE administration induced a decrease in CD44 + splenic T-cells and CD45RB high , CD54 + blood and splenic T-cells. Conversely, the number of CD45RB low splenocytes was increased. Interestingly, the progressive increase in serum TNF-α and IFN-γ levels normally seen with age in these mice was inhibited by TCE. There was also a relative lower incidence of histological changes in the pancreas of TCE-exposed NOD mice than in unexposed mice. Contrary to what has been found in systemic models of autoimmunity, TCE did not accelerate the diabetes of NOD mice and may have a protective effect. This finding suggests that comparative studies using different genetically related autoimmune-prone models are needed to investigate the role of xenobiotics in the precipitation of autoimmunity, particularly in sensitive populations.

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“…CD4 ϩ T cells from patients with active lupus have hypomethylated DNA and overexpress LFA-1 on an autoreactive subset, which lyses autologous macrophages spontaneously [4 -6]. Methylation levels in thymus and lymphatic nodules of a murine model of lupus (MRL/lpr) were lower than those found in the MRL/ϩ strain [7]. Finally, CD4 ϩ T cells of mice treated with methylation inhibitors (5-azacitidina or procainamide) and transferred to syngenic mice induce a glomerulonephritis mediated by immunocomplexes, as well as IgG anti-DNA and antihistone antibodies [8].…”

Section: Introductionmentioning

confidence: 99%

Transcript overexpression of theMBD2andMBD4genes in CD4+ T cells from systemic lupus erythematosus patients

Balada

Ordi‐Ros

Serrano-Acedo

et al. 2007

Journal of Leukocyte Biology

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Global DNA hypomethylation in CD4+ T cells has been detected in systemic lupus erythematosus (SLE), and it seems to be linked to its pathogenesis. We investigated the relationship between overall DNA methylation and the expression of two methyl CpG-binding domain (MBD) proteins. DNA deoxymethylcytosine (d(m)C) content of purified CD4(+) T cells from 29 SLE patients and 30 healthy controls was measured by means of an ELISA. Transcript levels of two methyl CpG-binding proteins (MBD2 and MBD4) were quantified by real-time RT-PCR. Association studies were also carried out with several laboratory parameters, as well as with the patients' clinical manifestations. SLE patients had significantly less CD4+ T cell DNA d(m)C content than controls (0.802+/-0.134 vs. 0.901+/-0.133; P=0.007). MBD2 and MBD4 mRNA levels were considerably higher in the patients' group: 0.975 +/- 0683 versus 0.604 +/- 0.614 (P=0.004) and 0.359 +/- 0.330 versus 0.092 +/- 0.169, respectively (P<0.0005). It is interesting that SLE patients showed a negative correlation between methylation indices and MBD2 (r=-0.609, P<0.0005) and MBD4 (r=-0.395, P=0.034) transcript levels. MBD2 and MBD4 transcript overexpression and inverse correlations with DNA methylation indices indicate that both enzymes may really have a direct and active role on the genome-wide DNA hypomethylation observed in CD4+ T cells from SLE patients.

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Alteration of DNA methylation levels in MRL lupus mice

Cited by 32 publications

References 24 publications

DNA methylation: its contribution to systemic lupus erythematosus

DNA methylation: its contribution to systemic lupus erythematosus

Trichloroethylene Does Not Accelerate Autoimmune Diabetes in NOD Mice

Transcript overexpression of theMBD2andMBD4genes in CD4+ T cells from systemic lupus erythematosus patients

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