cs.tau.ac.il/expander/overview.html; Tel Aviv University,
Israel). PRIMA achieves www.selleckchem.com/products/gsk2656157.html this by utilizing known models for transcription factor binding sites. Corresponding transcription regulators are considered to be candidate regulators of the corresponding set of genes. We used Ingenuity Pathway Analysis (IPA, http://www.ingenuity.com) as described in detail previously [25] to identify de novo molecular networks that are associated with the NOD altered genes. We compared the whole genome mRNA expression in CD4 T-cells from 2-, 3-, and 4-week old NOD mice to that of two matched control strains, NOR and C57BL/6 (C57). NOR shares ∼88% of its genome with NOD mice, including the diabetogenic H2g7 MHC haplotype and several important
non-MHC T1D susceptibility loci [ [1], [2], [3] and [4], 29]. C57, on the other hand, is a more genetically distantly related strain to NOD. Yet, like C57, NOR is both insulitis- and diabetes-free. We identified 362, 982, and 581 probe sets (genes) with highly significant expression differences between strains (p < 0.005, Benjamini–Hochberg; FDR of 0.5%) at 2, 3, and 4 weeks, respectively. As expected, the majority of these genes had a similar pattern of expression in NOD and NOR compared to C57 ( Fig. 1). The focus of our study was to identify genes in NOR mice whose expression was similar to that in C57 but different from that in NOD, i.e. genes differentially expressed Ribociclib in NOD relative to both NOR and C57, and herein referred to as NOD altered genes. These constitute prospective candidate genes for protection of NOR mice against diabetes.
Thus, we identified a total of 58, 115, and 65 probe sets whose expression was altered in NOD at 2, 3 and 4 weeks, respectively, compared to both controls (clusters of lower or higher expression in NOD are indicated by arrows in Fig. 1). These represented 56, 107, and 60 different genes, respectively, shown in Table 1, Table 2, Table 3 and Table 4. The great majority of these genes were of lower expression in NOD mice compared to controls: ∼70% at 2 weeks; ∼72% at 3 weeks; and ∼87% at 4 weeks. Twenty-five genes (72% of which was of lower expression in NOD mice) were common Pembrolizumab research buy to all 3 ages. Results for qRT-PCR validation of eight genes are shown in Fig. S1 (3 of higher expression in NOD mice: protein tyrosine phosphatase 4a2 (Ptp4a2), biogenesis of organelles complex-1, subunit 6 (Bloc1s6, pallidin) and transmembrane protein 87A (Tmem87a); and 5 of lower expression in NOD mice: tripartite motif-containing 5 (Trim5), tripartite motif-containing 12A (Trim12a), Gatm (glycine amidinotransferase (l-arginine:glycine amidinotransferase)), lymphocyte antigen 6 complex, locus C1 (Ly6c1), and receptor transporter protein 4 (Rtp4) compared to control mice).
No related posts.