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PBC tissue- and age-specific changes in gene expression during disease induction and progression in NOD mice.

ABSTRACT: 41K whole genome oligo-microarrays (Agilent Technologies) were used to characterize age-dependent changes in gene expression in peripheral blood cells (PBC) obtained from up to 8 individual NOD mice at 6 different time points (10 days (n=8), and 4 weeks (n=3), 8 weeks (n=7), 12 weeks (n=8), 16 weeks (n=7), and 20 weeks of age (n=4)), compared to NOD.B10 tissue controls. "Milestone Genes" are genes whose expression was significantly changed (approximately 3 fold) as the result of splicing or changes in transcript level. Milestone Genes were identified among genes within type one diabetes (T1D) susceptibility regions (Idd). Milestone Genes showing uniform patterns of changes in expression at various time points were identified. Potential T1D candidate genes were identified among Milestone Genes within Idd regions and/or hierarchical clusters. These studies identified tissue- and age-specific changes in gene expression that may play an important role in the inductive or destructive events of T1D.

ORGANISM(S): Mus musculus

PROVIDER: GSE21897 | GEO | 2010/05/21

SECONDARY ACCESSION(S): PRJNA126857

REPOSITORIES: GEO

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PBC tissue- and age-specific changes in gene expression during disease induction and progression in NOD mice.

Project description:41K whole genome oligo-microarrays (Agilent Technologies) were used to characterize age-dependent changes in gene expression in peripheral blood cells (PBC) obtained from up to 8 individual NOD mice at 6 different time points (10 days (n=8), and 4 weeks (n=3), 8 weeks (n=7), 12 weeks (n=8), 16 weeks (n=7), and 20 weeks of age (n=4)), compared to NOD.B10 tissue controls. "Milestone Genes" are genes whose expression was significantly changed (approximately 3 fold) as the result of splicing or changes in transcript level. Milestone Genes were identified among genes within type one diabetes (T1D) susceptibility regions (Idd). Milestone Genes showing uniform patterns of changes in expression at various time points were identified. Potential T1D candidate genes were identified among Milestone Genes within Idd regions and/or hierarchical clusters. These studies identified tissue- and age-specific changes in gene expression that may play an important role in the inductive or destructive events of T1D. NOD/LtJ (NOD), NOD.B10Sn-H2b/J (NOD.B10) female mice of multiple ages were used for this study. Six Groups of NOD mice were sacrificed at 10 days, and 4, 8, 12, 16, and 20 weeks of age and peripheral blood cells (PBC) were removed and prepared for mRNA analysis. Two Groups of 10 NOD.B10 mice [10 days (n=10) + 20 weeks of age (n=10)] were used as a tissue specific control. Gene (mRNA) expression was analyzed using the 41K Whole Mouse Genome Oligo Microarray Kit (Agilent Technologies), and gene expression data are processed (cy3: NOD, cy5: NOD.B10) and reported as normalized expression ratios: Log 10 (NOD processed signal / NOD.B10 processed signal) (Log ratio). 10days of age; PBC_10d (n=8), 4 weeks of age; PBC_4w (n=3), 8 weeks of age; PBC_8w (n=7), 12 weeks of age; PBC_12w (n=8), 16 weeks of age; PBC_16w (n=7), 20 weeks of age; PBC_20w (n=4)

2010-06-09 | E-GEOD-21897 | biostudies-arrayexpress

PLN tissue- and age-specific changes in gene expression during disease induction and progression in NOD mice.

Project description:41K whole genome oligo-microarrays (Agilent Technologies) were used to characterize age-dependent changes in gene expression in pancreatic lymph nodes (PLN) obtained from up to 7 individual NOD mice at 6 different time points (10 days (n=7), and 4 weeks (n=6), 8 weeks (n=4), 12 weeks (n=7), 16 weeks (n=6), and 20 weeks of age (n=5)), compared to NOD.B10 tissue controls. "Milestone Genes" are genes whose expression was significantly changed (approximately 3 fold) as the result of splicing or changes in transcript level. Milestone Genes were identified among genes within type one diabetes (T1D) susceptibility regions (Idd). Milestone Genes showing uniform patterns of changes in expression at various time points were identified. Potential T1D candidate genes were identified among Milestone Genes within Idd regions and/or hierarchical clusters. These studies identified tissue- and age-specific changes in gene expression that may play an important role in the inductive or destructive events of T1D. NOD/LtJ (NOD), NOD.B10Sn-H2b/J (NOD.B10) female mice of multiple ages were used for this study. Six Groups of NOD mice were sacrificed at 10 days, and 4, 8, 12, 16, and 20 weeks of age and pancreatic lymph nodes (PLN) were removed and prepared for mRNA analysis. Two Groups of 10 NOD.B10 mice [10 days (n=10) + 20 weeks of age (n=10)] were used as a tissue specific control. Gene (mRNA) expression was analyzed using the 41K Whole Mouse Genome Oligo Microarray Kit (Agilent Technologies), and gene expression data are processed (cy3: NOD, cy5: NOD.B10) and reported as normalized expression ratios: Log 10 (NOD processed signal / NOD.B10 processed signal) (Log ratio). 10days of age; PLN_10d (n=7), 4 weeks of age; PLN_4w (n=6), 8 weeks of age; PLN_8w (n=4), 12 weeks of age; PLN_12w (n=7), 16 weeks of age; PLN_16w (n=6), 20 weeks of age; PLN_20w (n=5)

2009-03-10 | E-GEOD-15150 | biostudies-arrayexpress

SPL tissue- and age-specific changes in gene expression during disease induction and progression in NOD mice.

Project description:41K whole genome oligo-microarrays (Agilent Technologies) were used to characterize age-dependent changes in gene expression in spleen (SPL) obtained from up to 5 individual NOD mice at 6 different time points (10 days (n=5), and 4 weeks (n=5), 8 weeks (n=3), 12 weeks (n=5), 16 weeks (n=4), and 20 weeks of age (n=5)), compared to NOD.B10 tissue controls. "Milestone Genes" are genes whose expression was significantly changed (approximately 3 fold) as the result of splicing or changes in transcript level. Milestone Genes were identified among genes within type one diabetes (T1D) susceptibility regions (Idd). Milestone Genes showing uniform patterns of changes in expression at various time points were identified. Potential T1D candidate genes were identified among Milestone Genes within Idd regions and/or hierarchical clusters. These studies identified tissue- and age-specific changes in gene expression that may play an important role in the inductive or destructive events of T1D.

2010-05-19 | GSE21884 | GEO

PLN tissue- and age-specific changes in gene expression during disease induction and progression in NOD mice.

2009-03-10 | GSE15150 | GEO

Genome-Wide Gene Expression Profiles in the Pancreatic Lymph Nodes of non-obese diabetic (NOD) mice

Project description:Type 1 diabetes (T1D) is a polygenic autoimmune disorder caused by autoreactive T cells that recognize pancreatic islet antigens and subsequently destroy insulin-producing β-cells. Pancreatic lymph nodes (PLN) are an essential site for the development of T1D, where tolerance to pancreatic self-antigens is first broken and the autoimmune responses are amplified. The purpose of this study was to identify candidate genes and pathways in the PLN that may contribute to the pathogenesis of T1D using a mouse model of T1D. Genome-wide gene expression was measured in individual NOD PLN at 10 days (n=6), 4 weeks (n=6) or 12 weeks of age (n=5), against a pooled sample of age-matched NOD.B10 PLN as the control (n≥6), using Agilent Whole Mouse Genome Microarrays.

2015-03-09 | E-GEOD-66658 | biostudies-arrayexpress

Effect of the Idd2 locus of B10 origin on the transcriptome of B cell of NOD mice

Project description:Type 1 diabetes (T1D) is an autoimmune disease characterized by pancreatic beta-cell destruction. It is a complex genetic trait driven by over 30 genetic loci with parallels between humans and mice. The NOD mouse spontaneously develops autoimmune diabetes and is widely used to identify insulin-dependent diabetes (Idd) genetic loci linked to diabetes susceptibility. While many Idd loci have been extensively studied, the impact of the Idd2 locus on autoimmune diabetes susceptibility remains to be defined. To address this, we generated a NOD congenic mouse bearing B10 resistance alleles on chromosome 9 in a locus coinciding with part of the Idd2 locus and find that NOD.B10-Idd2 congenic mice are highly resistant to diabetes. Bone marrow chimera and adoptive transfer experiments show that the B10 protective alleles provide resistance in an immune cell-intrinsic manner. While no T cell-intrinsic differences between NOD and NOD.B10-Idd2 mice were observed, we find that the Idd2 resistance alleles limit the formation of spontaneous and induced germinal centers. Comparison of the B cell transcriptome profile from NOD and NOD.B10-Idd2 mice reveal that resistance alleles at the Idd2 locus affect the expression of specific MHC molecules, a result confirmed by flow cytometry. Altogether, these data demonstrate that resistance alleles at the Idd2 locus impair germinal center formation and influence MHC expression, both of which likely contribute to reduce diabetes incidence.

2022-10-06 | GSE185487 | GEO

Gene expression in the islets of 10 day old, 4 week old and 12 week old Non-Obese Diabetic (NOD) mice vs. healthy, age-matched NOD.B10 control mice

Project description:Gene expression in the islets of NOD vs. NOD.B10 mice at 10 days, 4 weeks and 12 weeks of age insulitis.

2020-04-23 | GSE149086 | GEO

Gene expression in the pancreas of 12 week old Non-Obese Diabetic (NOD) mice vs. healthy age-matched NOD.B10 control mice

Project description:Gene expression in the pancreas of NOD vs. NOD.B10 mice at 12 weeks of age

2020-07-21 | GSE154739 | GEO

Gene expression in the islets of 12 wk old Non-Obese Diabetic (NOD) mice and healthy control NOD.B10 mice

Project description:Gene expression in the islets of NOD and NOD.B10 mice at 12 weeks of age, prior to the onset of destructive insulitis.

2013-04-10 | GSE45897 | GEO

A discovery-based proteomics approach identifies protein disulfide isomerase (PDIA1) as a biomarker of β cell stress in type 1 diabetes

Project description:Background: Activation of stress pathways intrinsic to the β cell are thought to both accelerate β cell death and increase β cell immunogenicity in type 1 diabetes (T1D). However, information on the timing and scope of these responses is lacking. Methods: To identify temporal and disease-related changes in islet β cell protein expression, SWATH-MS/MS proteomics analysis was performed on islets collected longitudinally from NOD mice and NOD-SCID mice rendered diabetic through T cell adoptive transfer. Findings: In islets collected from female NOD mice at 10, 12, and 14 weeks of age, we found a time-restricted upregulation of proteins involved in the maintenance of β cell function and stress mitigation, followed by loss of expression of protective proteins that heralded diabetes onset. Pathway analysis identified EIF2 signaling and the unfolded protein response, mTOR signaling, mitochondrial function, and oxidative phosphorylation as commonly modulated pathways in both diabetic NOD mice and NOD-SCID mice rendered acutely diabetic by adoptive transfer, highlighting this core set of pathways in T1D pathogenesis. In immunofluorescence validation studies, β cell expression of protein disulfide isomerase A1 (PDIA1) and 14-3-3b were found to be increased during disease progression in NOD islets, while PDIA1 plasma levels were increased in pre-diabetic NOD mice and in the serum of children with recent-onset T1D compared to age and sex-matched non-diabetic controls. Interpretation: We identified a common and core set of modulated pathways across distinct mouse models of T1D and identified PDIA1 as a potential human biomarker of β cell stress in T1D.

2023-03-11 | PXD035504 | Pride

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