ABSTRACT: Transcriptional analysis of concequent lack of rpS6 kinase activity in mice livers hepatocytes due to deletion of S6 kinases 1 and 2 (S6K1 and S6K2).
Project description:To obtain the molecular signature of the effect that the IL-2 therapeutic dose induces on T cells in vivo, we performed gene array analysis. Since it was critical to perform this analysis on highly purified Tregs and Teffs, and also because activated Teffs can acquire CD25 expression, we used GFP-Foxp3 knock-in mice which allow for the purification of Tregs and Teffs based on the GFP expression. Illumina gene array was carried out on FACS sorted CD4+ GFP+ (Tregs) and CD4+ GFP- (Teffs) of mice that received either PBS or the curative schedule of IL-2, 2 hours after the last injection.
Project description:We previously showed that eRF3a depletion in the human colon carcinoma cell line HCT116 p53+/+ induces mTOR signaling pathway inhibition (Chauvin et al., 2007) suggesting that eRF3a belongs to a regulatory mechanism that modulate mTOR activity. However, this mechanism and the precise role of eRF3a remain to be determined. Here, to elucidate the mechanism dictating mTOR signaling pathway inhibition, we aimed to define the transcript expression and polysome profiles of HCT116 cells after short interfering RNA (siRNA)-mediated depletion of eRF3a. Three days after HCT116 cells electroporation with either sh-3a1 which was previously shown for effectively silence eRF3a (Chauvin et al., 2005) or control shRNA (sh-Ctrl), total and polysome-associated RNAs were extracted and we conducted a microarray analysis of differentially expressed genes using the Illumina HumanHT-12 Expression BeadChips.
Project description:Analysis of synoviocytes cell form patients suffering of Rheumatoid arthritis and depleted for clusterin by siRNA knockdown. Note: this experiment was reloaded into ArrayExpress on 2nd December 2009 because the incorrect array design had originally been selected. The identifiers in the datafile were also fixed to match the array design.
Project description:Administration of low-dose IL-2 prevents and cures type 1 diabetes (T1D) in NOD mice by boosting pancreatic regulatory T cells (Tregs) and is currently being evaluated in humans. Here, to improve treatment efficacy we tested higher IL-2 doses that, despite further boosting Tregs, rapidly precipitated T1D in pre-diabetic mice due to generalized immune activation. Although the combination of rapamycin (RAPA) plus IL-2 prevents NOD T1D development, a recent clinical trial translating this strategy into patients was halted due to C-peptide decline. Here, we show that RAPA/IL-2 combination was also ineffective to cure new onset T1D in mice and, surprisingly, RAPA broke IL-2-induced tolerance in a reversible way. RAPA partially counteracted IL-2 effects on Tregs and the combined treatment unexpectedly, impaired glucose homeostasis at multiple levels, possibly explaining the clinical outcome. Our data help understand IL-2 alone or RAPA/IL-2 combination limitations and could lead to the design of improved T1D therapies.
Project description:Direct comparison of gene expression in 13.5dpc embryonic gonad/mesonephros between male Mrotm1H/Mrotm1H mice and male wild-type littermates. Two independent pools of 10 gonads (5 mice) were compared on 4 microarrays (two colourswaps).
Project description:A comparison of Ky mouse mutant soleus muscles versus wildtype soleus muscles. Hybridisation of 3 Mouse SGC 7.5k oligo slides, using 3 independent pools of 10 mice (5 male, 5 female)for both WT and mutant animals.
Project description:A comparison of Ostesy mutant soleus muscles to wildtype soleus muscles. Hybridisation of 3 Mouse SGC 7.5k oligo arrays, using 3 pools of 10 mice(5 male and 5 female) for mutant and WT.
Project description:Microarray technology was used to monitor the level of expression of 9,300 human genes at different time-points after infection of the type II alveolar A549 human cell line with HRSVs.