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Over expression of mRNA for multiple genes including insulin in the PLN of NOD is associated with Islet Autoimmunity

ABSTRACT: The aim of this study is to identify genes implicated in the early steps of the autoimmune process, prior to inflammation in type 1 diabetes. Early Insulin AutoAntibodies (E-IAA) have been used as subphenotypic marker to select individual animals as type 1 diabetes prone and to compare gene expression patterns with insulin autoantibody negative NOD. Variation of gene expression patterns in the pancreatic lymph nodes (PLN) issued from E-IAA positive and negative mice have been analyzed by DNA microarrays

ORGANISM(S): Mus musculus

PROVIDER: GSE15582 | GEO | 2009/10/02

SECONDARY ACCESSION(S): PRJNA115587

REPOSITORIES: GEO

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Over expression of mRNA for multiple genes including insulin in the PLN of NOD is associated with Islet Autoimmunity

Project description:The aim of this study is to identify genes implicated in the early steps of the autoimmune process, prior to inflammation in type 1 diabetes. Early Insulin AutoAntibodies (E-IAA) have been used as subphenotypic marker to select individual animals as type 1 diabetes prone and to compare gene expression patterns with insulin autoantibody negative NOD. Variation of gene expression patterns in the pancreatic lymph nodes (PLN) issued from E-IAA positive and negative mice have been analyzed by DNA microarrays PLN were used from 5 weeks old NOD mice positive for Insulin Autoantibodies and compared with animals negative for Insulin AutoAntibodies

2009-10-02 | E-GEOD-15582 | biostudies-arrayexpress

Genome-Wide Gene Expression Profiles in the Pancreatic Lymph Nodes of At-Risk Autoantibody Positive Individuals

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. Microarray analysis was performed on the PLN of human non-diabetic healthy controls (n=7) and at-risk autoantibody-positive subjects (n=13).

2015-03-03 | E-GEOD-66413 | biostudies-arrayexpress

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

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

2015-03-09 | GSE66658 | GEO

Genome-wide expression kinetics of children with T1D-associated autoantibodies compared to healthy matched controls I

Project description:To unravel genes and molecular pathways involved in the pathogenesis of type 1 diabetes (T1D), we performed genome-wide gene expression profiling of prospective venous blood samples from children developing T1D-associated autoantibodies or progressing towards clinical diagnosis. 63 peripheral blood RNA samples from 6 autoantibody-positive children (Case) and their matched controls (Control) were analyzed with Illumina Sentrix WG-6 v2 genome-wide arrays, in order to study the gene expression changes occuring during the pathogenesis of Type 1 diabetes (T1D). Each case child (positive for T1D-specific autoantibodies) was matched with a persistently autoantibody-negative control child, with the same HLA-DQB1 risk category, gender, and place and date of birth. Seroconversion is determined as the first detection of T1D-specific autoantibody/autoantibodies (ICA titre >4 JDFU, IAA >3.47 RU, GADA >5.4 RU, IA-2A >0.43 RU, ZnT8A >0.61 RU).

2014-02-20 | E-GEOD-30208 | biostudies-arrayexpress

Genome-wide expression kinetics of children with T1D-associated autoantibodies compared to healthy matched controls II

Project description:To unravel genes and molecular pathways involved in the pathogenesis of type 1 diabetes (T1D), we performed genome-wide gene expression profiling of prospective venous blood samples from children developing T1D-associated autoantibodies or progressing towards clinical diagnosis. 58 peripheral blood RNA samples from 4 autoantibody-positive children and their matched controls were analyzed with Illumina Sentrix WG-6 v2 genome-wide arrays, in order to study the gene expression changes occuring during the pathogenesis of Type 1 diabetes (T1D). Each case child (positive for T1D-specific autoantibodies) was matched with a persistently autoantibody-negative control child, with the same HLA-DQB1 risk category, gender, and place and date of birth. Seroconversion is determined as the first detection of T1D-specific autoantibody/autoantibodies (ICA titre >4 JDFU, IAA >3.47 RU, GADA >5.4 RU, IA-2A >0.43 RU, ZnT8A >0.61 RU).

2014-02-20 | E-GEOD-30209 | 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

Transgenic mice carrying the human PLN gene

Project description:These mice have been genetically modified so that the mouse PLN gene has been replace with the human PLN gene. Phopspholamban (PLN), the reversible inhibitor of the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a), is a key regulator of myocyte Ca2+-cycling with a significant role in heart failure. We previously showed that the single amino acid difference between human and mouse PLN results in increased inhibition of Ca2+-cycling, cardiac remodeling and attenuated stress responses, in transgenic mice expressing the human PLN in the null background (hPLN). This set of microarray experiments aimed at deciphering the molecular mechanisms implicated in this process.

2011-12-15 | GSE20172 | GEO

Genome-wide espression kinetics of children progressing to clinical Type 1 diabetes (T1D).

Project description:To unravel genes and molecular pathways involved in the pathogenesis of type 1 diabetes (T1D), we performed genome-wide gene expression profiling of prospective venous blood samples from children developing T1D-associated autoantibodies or progressing towards clinical diagnosis. 247 peripheral blood RNA samples from 18 prediabetic children and their matched controls were analyzed with Illumina Human HT-12 Expression BeadChips version 3 arrays, in order to study the gene expression changes occuring during the pathogenesis of Type 1 diabetes (T1D). Each case child (with T1D-specific autoantibodies) was matched with a persistently autoantibody-negative control child, with the same HLA-DQB1 risk category, gender, and place and date of birth. Two control children were selected for T1D cases 3, 5, 13 and 17. Seroconversion is determined as the first detection of T1D-specific autoantibody/autoantibodies (ICA titre >4 JDFU, IAA >3.47 RU, GADA >5.4 RU, IA-2A >0.43 RU, ZnT8A >0.61 RU).

2014-02-20 | E-GEOD-30210 | biostudies-arrayexpress

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