Project description:Because activation of the immune response is dependent on extensive changes in gene expression, it is likely that a major component of inter-individual variation in the immune response is ultimately mediated at the level of gene regulation. Here, we examine the influence of genetic variation on inducible gene expression in the murine immune response. We report strain-specific genome-wide differences in mRNA expression between NOD and B10 inbred mice in CD4 splenocytes in basal, stimulated (4hr, PMA/I) states.
Project description:Nonobese diabetic (NOD) mice congenic for B10 derived genes in the Idd9 region of chromosome 4 are highly protected from the development of diabetes. In order to identify possible candidate genes within the Idd9 susceptibility region and possible downstream mediators of protection, we compared gene expression between NOD and Idd9 CD4+ T-cells. CD4+ T-cells with an activated phenotype (CD44-high/CD62L-low) were sorted from the pancreatic lymph nodes of female 8-week old mice. Mice were bred at Taconic farms and were line 905 (NOD.B10-Idd9 congenic) and line 6359 (NOD-like control strain with a B10 congenic region on chromosome 1 which does not modify diabetes incidence). Three replicate samples were prepared, each from four pooled pancreatic lymph nodes. CD4+CD44-highCD62L-low T-cells were sorted from each sample.
Project description:Cellular binary fate decisions require the progeny to silence genes associated with the alternative fate. The major subsets of alpha:beta T cells have been extensively studied as a model system for fate decisions. While the transcription factor RUNX3 is required for the initiation of Cd4 silencing in CD8 T cell progenitors, it is not required to maintain the silencing of Cd4 and other helper T lineage genes. The other runt domain containing protein, RUNX1, silences Cd4 in an earlier T cell progenitor, but this silencing is reversed whereas the gene silencing after RUNX3 expression is not reverse. Therefore, we hypothesized that RUNX3 and not RUNX1 recruits other factors that maintains the silencing of helper T lineage genes in CD8 T cells. To this end, we performed a proteomics screen of RUNX1 and RUNX3 to determine candidate silencing factors.
Project description:Nonobese diabetic (NOD) mice congenic for B10 derived genes in the Idd9 region of chromosome 4 are highly protected from the development of diabetes. In order to identify possible candidate genes within the Idd9 susceptibility region and possible downstream mediators of protection, we compared gene expression between NOD and Idd9 CD4+ T-cells. CD4+ T-cells with an activated phenotype (CD44-high/CD62L-low) were sorted from the pancreatic lymph nodes of female 8-week old mice.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
