Dataset: Molecular Phenotyping of Immune Cells from Young NOD Mice

Islet leukocytic infiltration (insulitis) is first obvious at around 4 weeks of age in the NOD mouse – a model for human type 1 diabetes (T1DM). The molecular events leading to insulitis are poorly understood. Since TIDM is caused by numerous genes, we hypothesized that multiple molecular pathways are altered and interact to initiate this disease. Analysis of the global gene expression profiles using microarrays followed by hierarchical clustering revealed that the majority (~90%) of the differentially expressed genes in NOD mice relative to control mice were repressed. Further analysis of these genes using a modern suite of multiple bioinformatics approaches identified abnormal molecular pathways that can be divided broadly into 2 categories: metabolic pathways, which were predominant at 2 weeks, and immune response pathways, which were predominant at 4 weeks. Network analysis by Ingenuity pathway analysis (IPA) identified several putative key genes/molecules that may play a role in regulating these pathways, including five that were common to both ages (TNF, HNF4A, IL15, Progesterone, and YWHAZ), and others that were unique to 2 weeks (e.g. MYC/MYCN, TGFB1, and IL2) and to 4 weeks (e.g. IFNG, beta-estradiol, p53, NFKB, AKT, PRKCA, IL12, and HLA-C). Spleen leukocytes were collected from NOD mice and two control strains, NON, and C57BL/6, at 2 and 4 weeks of age (n=5 for each strain and each age group). NON is the original diabetes-resistant control strain closely related genetically to the NOD strain, whereas C57BL/6 is a more distantly related strain with some immunogenetic similarities to NOD. RNA expression was analyzed on Affymetrix expression arrays MOE 430 A and MOE430B. The two arrays were combined prior to statistical analysis of the data giving a total of ~45,000 probe sets per sample.

Species:

mouse

Samples:

30

Source:

E-GEOD-37450

Updated:

Dec.12, 2014

Registered:

Nov.23, 2014