Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse transgenic for Aire expressing pancreatic islets

ABSTRACT: The aim of this study was to determine the effect of transgenic Aire expression on the transcriptional profile of a tissue that normally does not express Aire: pancreatic islets. The transcriptional profile of transgenic RIP-Aire27 islets was compared to non-transgenic littermate islets as well as to archival NOD thymic medullary epithelial cells (MEC) data. All data were from non-obese diabetic (NOD) mice Experiment Overall Design: 3-wk-old individual male RIP-Aire27 or non-transgenic littermates islets were isolated by gradient purification followed by hanpicking under a microscope for subsequent RNA purification, labeling and hybridization to Affymetrix arrays.

ORGANISM(S): Mus musculus

SUBMITTER: CBDM Lab

PROVIDER: E-GEOD-12073 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background. T cells in the thymus undergo opposing positive and negative selection processes so that the only T cells entering circulation are those bearing a T cell receptor (TCR) with a low affinity for self. The mechanism differentiating negative from positive selection is poorly understood, despite the fact that inherited defects in negative selection underlie organ-specific autoimmune disease in AIRE-deficient people and the non obese diabetic (NOD) mouse strain. Results. Here we use homogeneous populations of T cells undergoing either positive or negative selection in vivo together with genome-wide transcription profiling on microarrays to identify the gene expression differences underlying negative selection to an Aire-dependent organ-specific antigen, including the upregulation of a genomic cluster in the cytogenetic band 2F. Analysis of defective negative selection in the autoimmune-prone NOD strain demonstrates a global impairment in the induction of the negative selection response gene set, but little difference in positive selection response genes. Combining expression differences with genetic linkage data we identify differentially expressed candidate genes including Bim, Bnip3, Smox, Pdrg1, Id1, Pdcd1, Ly6c, Pdia3, Trim30 and Trim12. Conclusions. The data provide a molecular map of the negative selection response in vivo, and by analysis of deviations from this pathway in the autoimmune susceptible NOD strain, suggest that susceptibility arises from small expression differences in genes acting at multiple points in the pathway between the TCR and cell death. Experiment Overall Design: Analysis of two thymic populations - early single positive thymocytes (CD4+CD8lowCD69+TCRhi) and early double positive thymocytes (CD4+CD8+CD69-TCRlow). Samples purified from the 3A9 TCR transgenic (TCR) to characterise positive selection and the 3A9 TCR x insHEL double transgenic (Dbl) to characterise negative selection towards an Aire-dependent organ-specific antigen. Both the non autoimmune C57BL10.H2k (B10) and autoimmune Non obese diabetic (NOD) strains were analysed in this method. Three biological replicates were used for each of these eight different groups.

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Transcription profiling of mouse transgenic for Aire expressing pancreatic islets

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