Overlapping BXSB congenic intervals, in combination with microarray gene expression, reveal novel lupus candidate genes

Haywood, M; Rose, S.J.; Horswell, Stuart; Lees, MJ; Fu, Guoliang; Walport, Mark J.; Morley, Bernard J

doi:10.1038/sj.gene.6364294

Cited by 80 publications

(71 citation statements)

References 53 publications

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“…To confirm the differential expression patterns previously reported in whole splenocyte populations (13), analysis of expression in purified macrophage populations was performed. These data confirmed that low level expression of Marco was linked to the presence of the BXSB allele.…”

Section: S Ystemic Lupus Erythematosus (Sle)mentioning

confidence: 99%

“…To identify potential disease-associated candidate genes in these intervals, microarray expression profiling (13) was performed on the congenic strains and a number of differentially regulated genes were identified. Of these, Marco (macrophage receptor with collagenous structure) localizing to Bxs2 was a strong candidate.…”

Section: S Ystemic Lupus Erythematosus (Sle)mentioning

confidence: 99%

“…Global expression analysis was previously performed in each of the strains C57BL/10 (B10), BXSB, B10.Bxs1/4, B10.Bxs1, B10.Bxs1/2, B10.Bxs2/3, and B10.Yaa as described (13). The data are available on the Array Express website of the European Molecular Biology Laboratory/European Bioinformatics Institute (EMBL-EBI) database (www.ebi.ac.uk/microarray-as/ ae/), and the accession code is E-MIMR-7.…”

Section: Microarray Data Analysismentioning

confidence: 99%

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A Defect in Marco Expression Contributes to Systemic Lupus Erythematosus Development via Failure to Clear Apoptotic Cells

Rogers¹,

Lees

Gabriel³

et al. 2009

The Journal of Immunology

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Systemic lupus erythematosus is a multisystem autoimmune disease characterized by the production of numerous antinuclear autoantibodies and inflammatory mediators. The BXSB mouse strain is an excellent model of the disease. Previous work has determined a number of important disease susceptibility intervals that have been isolated in separate congenic strains. Here, we have combined expression data from those strains with functional analyses to demonstrate that reduced expression of the innate scavenger receptor Marco (macrophage receptor with collagenous structure) is a primary event in BXSB mice, that reduced mRNA expression is mirrored at the protein level, and that this results in a significant alteration in function. We have confirmed a role for Marco in the clearance of apoptotic cells and a generalized defect in both endocytosis and phagocytosis. The failure to clear apoptotic cells has previously been linked to the development of systemic lupus erythematosus. However, the use of congenic mice with limited phenotypes in this study has enabled us to propose that in the case of Marco at least, disease results from the production of anti-dsDNA Abs.

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Section: S Ystemic Lupus Erythematosus (Sle)mentioning

confidence: 99%

Section: S Ystemic Lupus Erythematosus (Sle)mentioning

confidence: 99%

Section: Microarray Data Analysismentioning

confidence: 99%

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A Defect in Marco Expression Contributes to Systemic Lupus Erythematosus Development via Failure to Clear Apoptotic Cells

Rogers¹,

Lees

Gabriel³

et al. 2009

The Journal of Immunology

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“…Previous studies have reported that human GAS5 was upregulated in osteoarthritis (OA) patients (8) and downregulated in certain cancer types, including breast cancer (9), renal cell carcinoma (10) and hepatocellular cancer (11). The GAS5 gene locus in the mouse BXSB strain has been linked to increased susceptibility to SLE (12). GAS5 competes with glucocorticoid (GC) response elements (GRE) by interacting with the DNA binding domain of glucocorticoid receptors (GRs).…”

Section: Introductionmentioning

confidence: 99%

Association of long non‑coding RNA GAS5 and miR‑21 levels in CD4+ T cells with clinical features of systemic lupus erythematosus

et al. 2017

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Abstract. The present study aimed to assess the expression of growth arrest-specific 5 (GAS5) and microRNA (miR)-21 in systemic lupus erythematosus (SLE), and attempted to explore their association with clinical features. CD4 + T cells were isolated from peripheral blood of healthy donors and SLE patients by magnetic-activated cell sorting. GAS5 and miR-21 expression levels in cluster of differentiation (CD)4 + T cells were measured by reverse-transcription quantitative polymerase chain reaction. The results revealed that GAS5 and miR-21 levels were significantly elevated in CD4 + T cells of patients with SLE compared with those in control subjects (P<0.05). Regarding clinical features, SLE patients with ulceration had higher GAS5 expression levels in CD4 + T cells than those without ulceration (P<0.05), and the expression of miR-21 was significantly higher in CD4 + T cells of SLE patients with low levels of complement component 3 (C3) than in those with normal levels of complement C3 (P<0.05).In conclusion, GAS5 and miR-21 in CD4 + T cells may serve as potential biomarkers for the diagnosis and monitoring of the progression of SLE. IntroductionSystemic lu pus erythematosus (SLE) is a multisystemic, chronic inflammatory autoimmune disease of unknown etiology. It is characterized by various pathogenic autoantibodies and immune complexes as well as damage to multiple organ systems, and the course of SLE is long followed by remission and acute attack. The prevalence varies from 31-70/100,000 individuals in China and from 20-70/100,000 individuals worldwide. It is sex-associated, occurring nine times more often in women than in men, particularly in women of child-bearing age (15-35 years) (1-3). The interaction between certain genetic and environmental factors, including chemical factors, viruses and drugs, damages normal immune tolerance and contributes to SLE. Dysfunctional T cells interact with new antigens constantly, leading to a persistent autoimmune reaction (4,5). Previous studies have confirmed that the abnormal activation and proliferation of self-reactive cluster of differentiation (CD)4 + T lymphocytes have a central role in SLE. CD4 + T cells interact with antigen-specific B cells, to make the latter ones become more effective and produce autoantibodies. In addition, CD4 + T cells produce various cytokines when they are activated, which may engender inflammatory reactions (6,7).Long non-coding RNAs (lncRNAs) are a class of non-protein-coding RNA with transcripts longer than 200 nucleotides. They have numerous important biological functions through different molecular mechanisms, and are closely associated with a variety of clinical diseases, including tumors, metabolic disease and autoimmune diseases. Growth arrest-specific 5 (GAS5), a non-coding gene that hosts a number of small nucleolar RNAs, has been suggested to have numerous important roles in apoptosis and cell growth inhibition. Previous studies have reported that human GAS5 was upregulated in osteoarthritis (OA) patients (8) and downregulated i...

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“…Suppressed GAS5 may inhibit the cell cycle and apoptosis. Therefore, it is implicated in autoimmune diseases by leading promotion antigen exposure and production of autoantibodies (57). The GWAS have identified a region on chromosome 1q25 that is associated with SLE.…”

Section: Noncoding Rnas and Slementioning

confidence: 99%

Epigenetics in systemic lupus erythematosus

Xiao

Zuo

2015

Biomedical Reports

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Abstract. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, with mechanisms that remain to be elucidated. Previous studies have proposed that genes and environments are required for lupus to develop and flare. It has been found that epigenetics have a significant influence on SLE. The present review will concentrate on epigenetics in SLE. There are a number of studies reporting that autoreactive T cells and B cells in patients with SLE have evidence of altered patterns of DNA methylation, modifications of histones and microRNA (miRNA). Long noncoding RNAs (lncRNAs) are another type of noncoding RNAs, which have an important role in epigenetics. lncRNAs may possibly become a new hotspot in SLE.

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Overlapping BXSB congenic intervals, in combination with microarray gene expression, reveal novel lupus candidate genes

Cited by 80 publications

References 53 publications

A Defect in Marco Expression Contributes to Systemic Lupus Erythematosus Development via Failure to Clear Apoptotic Cells

A Defect in Marco Expression Contributes to Systemic Lupus Erythematosus Development via Failure to Clear Apoptotic Cells

Association of long non‑coding RNA GAS5 and miR‑21 levels in CD4+ T cells with clinical features of systemic lupus erythematosus

Epigenetics in systemic lupus erythematosus

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