Probe sets of unknown identification/function are listed under “Unknown”. Based on these categories, a higher percentage of NOD altered genes (∼22%) were involved in apoptosis/cellular proliferation at each of 2 or 3 weeks than at 4 weeks (12%). Conversely, a higher percentage

of genes (22%) were involved in immune response at 4 weeks than at 2 or 3 weeks (4.1% and 12%, respectively). Overall, a high percentage of genes at all 3 ages were involved in enzymatic activity, including several kinases/phosphatases at 3 weeks. Moreover, a large number of the CD4 T-cell NOD altered genes lie within known Idds, 52%, RO4929097 47% and 38% at 2, 3, and 4 weeks, respectively ( Table 1, Table 2, Table 3 and Table 4). A total of 14 (25%),

20 (∼19%) and 10 (∼17%) genes at 2, 3, and 4 weeks, respectively, lie within Idd13, a region located on chromosome (Chr) 2 and previously identified to confer resistance to diabetes in NOR mice [ 4, [15], [16] and [17], 30]. These genes included 6 that were common to all 3 ages: Bloc1s6, Venetoclax order Trp53bp1 (transformation related protein 53 binding protein 1), Tmem87a, Ctdspl2 (CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) small phosphatase like 2), Gatm and Raly (hnRNP-associated with lethal yellow). Two genes (Khdrbs1 − KH domain containing, RNA binding, signal transduction associated 1 and Ptp4a2, both altered at 2 and 3 weeks, but only Khdrbs1 at 4 weeks) lie within Idd9/11, a region on Chr4 that also confers resistance to diabetes in NOR. This region has also been demonstrated previously by several groups Exoribonuclease to regulate the diabetogenic activity of CD4 T-cells [ 5, 10, 18, 19]. To gain further insights into the biological processes associated with the NOD altered genes, we performed Gene ontology (GO) and KEGG pathway analyses. Because GO analysis is better suited for larger gene lists, we also analyzed gene lists generated

at a slightly lower statistical stringency. Analysis at p < 0.05, Benjamini–Hochberg (FDR of 5%) identified 134, 252, and 185 NOD altered genes at 2, 3, and 4 weeks, respectively ( Tables S2, S3 and S4, respectively). The topmost ranked major biological process of these gene lists was metabolism ( Table 5). Although common to all 3 ages, this functional category was most significantly enriched at 2 weeks. Several biological processes unique to 3 weeks were also identified, including biopolymer modification, localization and transport, and T cell activation. Under “molecular function”, hydrolase activity and binding were the common top ranked categories. “Intracellular” was the most significantly enriched cellular component for all the 3 lists. Nucleus and cytoplasm/endoplasmic reticulum were uniquely enriched at 2 and 3 weeks, respectively.