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Mapping the Transcriptional Landscape of Autoimmune Targeted Tissues: Transient Alterations in the Extracellular Milieu Precede Innate and Delayed Adaptive Immune Responses in Spontaneous Experimental Autoimmunity.

ABSTRACT: The C57BL/6.NOD-Aec1Aec2 mouse is a model for primary Sjögren’s syndrome and was constructed by introducing two genetic intervals derived from the NOD mouse that confers Sjögren’s syndrome (SjS)-like disease in SjS-non-susceptible C57BL/6 mice. To define the chronological interrelationships of biological themes associated with progression from pre- to sub-clinical to overt spontaneous experimental SjS-like disease involving the extracellular milieu (EM) of the salivary glands, we carried out a study utilizing microarray technology in which the parental C57BL/6J mouse was used as the healthy control strain. A bioinformatics-based data analysis methodology designed for comprehensive visualization of global datasets between C57BL/6J and C57BL/6.NOD-Aec1Aec2 mice has permitted a definition of the molecular changes that correlate with onset of stomatitis sicca (xerostomia) in the SjS-susceptible mice. The transcriptome data set of C57BL/6J permitted identification of normal physiological activity.

ORGANISM(S): Mus musculus

PROVIDER: GSE36378 | GEO | 2012/03/10

SECONDARY ACCESSION(S): PRJNA153259

REPOSITORIES: GEO

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Salivary gland during development and onset of xerostomia in murine model of Sjögren's syndrome-like disease

Project description:Differential gene expression in the salivary gland during development and onset of xerostomia in Sjögren’s syndrome-like disease of the C57BL/6.NOD-Aec1Aec2 mouse. Recently, we reported the development of the C57BL/6.NOD-Aec1Aec2 mouse that carries two genetic intervals derived from the NOD mouse capable of conferring Sjögren’s syndrome (SjS)-like disease in SjS-non-susceptible C57BL/6 mice. In an attempt to define the molecular bases underlying onset of stomatitis sicca (xerostomia) in this C57BL/6.NOD-Aec1Aec2 mouse model, we have carried out a study utilizing microarray technology.

2009-04-11 | GSE15640 | GEO

Mapping the Transcriptional Landscape of Autoimmune Targeted Tissues: Transient Alterations in the Extracellular Milieu Precede Innate and Delayed Adaptive Immune Responses in Spontaneous Experimental Autoimmunity.

Project description:The C57BL/6.NOD-Aec1Aec2 mouse is a model for primary SjM-CM-6grenM-bM-^@M-^Ys syndrome and was constructed by introducing two genetic intervals derived from the NOD mouse that confers SjM-CM-6grenM-bM-^@M-^Ys syndrome (SjS)-like disease in SjS-non-susceptible C57BL/6 mice. To define the chronological interrelationships of biological themes associated with progression from pre- to sub-clinical to overt spontaneous experimental SjS-like disease involving the extracellular milieu (EM) of the salivary glands, we carried out a study utilizing microarray technology in which the parental C57BL/6J mouse was used as the healthy control strain. A bioinformatics-based data analysis methodology designed for comprehensive visualization of global datasets between C57BL/6J and C57BL/6.NOD-Aec1Aec2 mice has permitted a definition of the molecular changes that correlate with onset of stomatitis sicca (xerostomia) in the SjS-susceptible mice. The transcriptome data set of C57BL/6J permitted identification of normal physiological activity. The study was designed to define the changing gene expression profiles within the salivary glands of C57BL/6.NOD-Aec1Aec2 mice at multiple time points representing a pre-disease stage (4 weeks), the early pre-clinical stage (8 weeks), the initial influx of leukocytes into the salivary glands (12 weeks), and the early clinical phase of autoimmunity (16 weeks) to characterize the influence of the extracellular milieu on early development of disease. Because the C57BL/6.NOD-Aec1Aec2 mouse was derived from the C57BL/6J line, C57BL/6J mice were used as the comparative healthy controls. This comparison permitted the identification of disease-associated gene expressions by subtracting out normal physiological processes. This present study represents the C57BL/6J healthy control mice. Series GSE15640 includes the data for the C57BL/6.NOD-Aec1Aec2 mice.

2012-03-10 | E-GEOD-36378 | biostudies-arrayexpress

Differential gene expression in the Lacrimal gland during development and onset of xerostomia in Sjögren’s syndrome-like disease of the C57BL/6.NOD-Aec1Aec2 mouse.

2013-06-25 | GSE48139 | GEO

Salivary gland during development and onset of xerostomia in murine model of SjM-CM-6gren's syndrome-like disease

Project description:Differential gene expression in the salivary gland during development and onset of xerostomia in SjM-CM-6grenM-bM-^@M-^Ys syndrome-like disease of the C57BL/6.NOD-Aec1Aec2 mouse. Recently, we reported the development of the C57BL/6.NOD-Aec1Aec2 mouse that carries two genetic intervals derived from the NOD mouse capable of conferring SjM-CM-6grenM-bM-^@M-^Ys syndrome (SjS)-like disease in SjS-non-susceptible C57BL/6 mice. In an attempt to define the molecular bases underlying onset of stomatitis sicca (xerostomia) in this C57BL/6.NOD-Aec1Aec2 mouse model, we have carried out a study utilizing microarray technology. The present study was designed to define the changing gene expression profiles within the salivary glands of C57BL/6.NOD-Aec1Aec2 mice at five time points representing a pre-disease stage (4 weeks), the early pre-clinical stage (8 weeks), the initial influx of leukocytes into the salivary glands (12 weeks), the early clinical phase of autoimmunity (16 weeks), and the early onset of clinical SjSlike disease characterized by secretory dysfunction (20 weeks). The C57BL/6.NOD-Aec1Aec2 mouse is a model of primary SjS in which the Idd3 region of chromosome 3 and the Idd5 region of chromosome 1 derived from the NOD mouse were bred into the non-autoimmune C57BL/6 mouse, resulting in a SjS-like disease susceptibility that mimics both the pathophysiological characteristics and reduced secretory responses observed with NOD mice during development and onset of disease. This SjS-susceptible strain was designated C57BL/6.NOD-Aec1Aec2, where Aec1 corresponds to Idd3 (of chromosome 3) and Aec2 corresponds to Idd5 (of chromosome 1).

2009-04-11 | E-GEOD-15640 | biostudies-arrayexpress

Differential gene expression in the Lacrimal gland during development and onset of xerostomia in Sjogren's syndrome-like disease of the C57BL/6.NOD-Aec1Aec2 mouse.

Project description:Recently, we reported the development of the C57BL/6.NOD-Aec1Aec2 mouse that carries two genetic intervals derived from the NOD mouse capable of conferring Sjogren's syndrome (SjS)-like disease in SjS-non-susceptible C57BL/6 mice. In an attempt to define the molecular bases underlying onset of stomatitis sicca (xerostomia) in this C57BL/6.NOD-Aec1Aec2 mouse model, we have carried out a study utilizing genomic microarray technology. The present study was designed to define the changing gene expression profiles within the Lacrimal glands of C57BL/6.NOD-Aec1Aec2 mice at five time points representing a pre-disease stage (4 weeks), the early pre-clinical stage (8 weeks), the initial influx of leukocytes into the Lacrimal glands (12 weeks), the early clinical phase of autoimmunity (16 weeks), and the early onset of clinical SjS-like disease characterized by secretory dysfunction (20 weeks). The C57BL/6.NOD-Aec1Aec2 mouse is a model of primary SjS in which the Idd3 region of chromosome 3 and the Idd5 region of chromosome 1 derived from the NOD mouse were bred into the non-autoimmune C57BL/6 mouse, resulting in a SjS-like disease susceptibility that mimics both the pathophysiological characteristics and reduced secretory responses observed with NOD mice during development and onset of disease. This SjS-susceptible strain was designated C57BL/6.NOD-Aec1Aec2, where Aec1 corresponds to Idd3 (of chromosome 3) and Aec2 corresponds to Idd5 (of chromosome 1).

2013-06-25 | E-GEOD-48139 | biostudies-arrayexpress

Transcription profiling by array of parotid tissue from Primary Sjögren’s Syndrome and controls

Project description:Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease with complex etiopathogenesis. Here we use Affymetrix U133 plus 2.0 microarray gene expression data from human parotid tissue. Parotid gland tissues were harvested from 17 pSS and 14 14 non-pSS sicca patients and 18 controls. The data were used in the following article: Nazmul-Hossain ANM, Pollard RPE, Kroese FGM, Vissink A, Kallenberg CGM, Spijkervet FKL, Bootsma H, Michie SA, Gorr SU, Peck AB, Cai C, Zhou H, Horvath S, Wong DTW (2012) Systems Analysis of Primary Sjögren’s Syndrome Pathogenesis in Salivary Glands: Comparative Pathways and Molecular Events in Humans and a Mouse Model. Parotid gland tissues were harvested from 17 pSS and 14 non-pSS sicca patients and 18 controls.

2012-09-06 | E-GEOD-40611 | biostudies-arrayexpress

Transcription profiling of human CD14+ CD16- and CD14low CD16+ monocytes from patients with Sjogrens syndrome and normal controls

Project description:Sjogren's syndrome is an autoimmune disease, characterized by complaints such as xerostomia and keratoconjunctivitis sicca. In other autoimmune diseases such as diabetes and SLE, monocyte abberancies have been described. Therefore, this study aimed at studying the monocyte compartment in Sjogren's Syndrome, by transcription profiling of CD14+CD16- and CD14lowCD16+ monocytes in patients and controls.

2008-08-04 | E-MEXP-1242 | biostudies-arrayexpress

Transcriptomic analysis of B cells from patients with Sjögren’s Syndrome

Project description:Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and prominent B cell hyperactivity. B cells are crucial in the pathophysiology of pSS through several mechanisms, including cytokine production, exocrine gland destruction, and autoantibody secretion. Considering the central role of B cells we performed RNA-sequencing analysis of circulating CD19+ B cells from patients with pSS, non-Sjögren’s sicca (nSS), and healthy controls (HC).

2022-12-14 | GSE199868 | GEO

Mus musculus

Project description:Differential gene expression in the Lacrimal gland during development and onset of xerostomia in Sjögren’s syndrome-like disease of the C57BL/6.NOD-Aec1Aec2 mouse.

| PRJNA209303 | ENA

Early detection of extranodal marginal zone lymphoma in Sjögren's syndrome patients through immunogenetics

Project description:Activated B cells play a key role in the pathogenesis of Sjögren’s syndrome (SjS) through the production of autoantibodies and the development of ectopic germinal centers in the salivary glands and other affected sites. Around 5-10% of SjS patients develop B-cell lymphoma, usually extranodal marginal zone lymphomas (eMZL) of the mucosa-associated lymphoid tissue (MALT). The aim of the current study is to screen for the eMZL clonotype in prediagnostic blood and tissue biopsies of SjS patients. We studied prediagnostic tissue biopsies of 3 SjS patients diagnosed with eMZL through immunoglobulin (IG) gene repertoire sequencing. In all 3 cases, we observed the eMZL clonotype in prediagnostic tissue biopsies. To evaluate if skewing in the IGH repertoire may also be detected in the peripheral blood, we sequenced a peripheral blood mononuclear cell (PBMC) sample drawn at eMZL diagnosis and 2 years prior to eMZL relapse in two SjS patients. The eMZL clonotype was detected in the peripheral blood prior to diagnosis for both cases. Next, we selected 3 SjS patients who developed eMZL lymphoma and 3 additional SjS patients who remained cancer-free. We sequenced the IG heavy chain (IGH) gene repertoire in PBMC samples taken a median of 3 years before eMZL diagnosis. In 2 out of 3 eMZL patients, the dominant clonotype in the prediagnostic PBMC samples matched the eMZL clonotype in the diagnostic biopsy. The eMZL clonotypes observed utilized stereotypic IGHV gene combinations (IGHV1-69/IGHJ4 and IGHV4-59/IGHJ5) associated with rheumatoid factor activity, a previously reported feature of eMZL in SjS. Notably, no significant abnormalities were observed in the IGH gene repertoire of the controls. In conclusion, our results indicate that immunogenetic sequencing of the IGH gene repertoire may be an effective method of early detection of eMZL in SjS patients.

2023-04-12 | GSE221412 | GEO

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