Microarray analysis of the skin of P2.5 K5cre-caNrf2 mice
Ontology highlight
ABSTRACT: The Nrf2 transcription factor is a key player in the cellular stress response, which regulates the expression of important antioxidant enzymes and other cytoprotective proteins. We recently generated a novel transgenic mouse model to determine the function of Nrf2 in the skin. These mice show reduced number of apoptotic keratinocytes after UVB irradiation due to enhanced ROS detoxification. They also show enhanced tumorigenesis in the HPV8 tumor model. RNA from whole skin of 3 single P2.5 K5cre-caNrf2 (tg/tg) and 3 single P2.5 K5cre-wt (tg/wt=control) mice were used
Project description:The Nrf2 transcription factor is a key player in the cellular stress response, which regulates the expression of important antioxidant enzymes and other cytoprotective proteins. We recently generated a novel transgenic mouse model to determine the function of Nrf2 in the skin. These mice revealed interesting phenotypic abnormalities, including hyperkeratosis and acanthosis. To gain insight into the underlying molecular mechanisms, we wanted to identify genes, which are differentially expressed in the skin of wild-type and mutant mice before the onset of phenotypic abnormalities. RNA from whole skin of 3 single P2.5 K5cre-caNrf2 (tg/tg) and 3 single P2.5 K5cre-wt (tg/wt=control) mice were used
Project description:Nrf2-regulated mRNAs are known; however, no Nrf2-regulated miRs have been identified miR microarray analysis from total RNA samples was performed to test which miRs are regulated by Nrf2 Total RNA from skin of mice with constitutively active Nrf2 (CMV-caNrf2), dominant-negative Nrf2 (dnNrf2), and correcponding control littermates (K5Cre(wt) for CMV-caNrf2 and wt for dnNrf2)
Project description:Purpose: The goals of this study are to identify dysregulated mRNAs in the heart after deletion of miR-1-1 and miR-1-2. Methods: Total RNAs were extracted from hearts at embryonic E15.5 (E15.5) or postnatal 2.5 days (P2.5) of miR-1s dHET and miR-1s dKO mice. mRNAs were purified using a poly-A selection approach and sequenced using Illumina HiSeq 2000. The sequence reads were aligned to the mouse reference genome (NCBI Build 37/mm9) using TopHat program (Bowtie algorithm). Transcript assembles and identification of differentially expressed genes were achieved using Cufflinks package. To account for expression bias due to transcript length, each sample transcript expression was normalized by using cufflinks algorithm with a FDR of 0.05. Results: Using 1.5-fold change as a cutoff, 997 and 653 transcripts were found to be upregulated and downregulated, respectively, in miR-1s dKO heart at P2.5. 423 transcripts were found to be upregulated and 653 were down-regulated in miR-1s dKO heart at E15.5. Many upregulated genes are directly involved in a fetal gene program. Conclusions: miR-1 directly represses a fetal gene program. We performed RNA deep-seq using postnatal 2.5 days (P2.5) heart from miR-1-1 and miR-1-2 double knockout mice and compared it to that of littermate control.
Project description:Cerebral Amyloid Angiopathy (CAA) is a significant comorbidity in almost all cases of Alzheimer’s disease (AD) and is unaddressed by current treatment regimens. We explored the Tg-SwDI mouse model which expresses human Amyloid Precursor Protein with the familial Swedish AD mutation as well as the vasculotropic Dutch and Iowa mutations leading to a phenotype of cognitive deficits with severe CAA. This is the first mapping of cerebral parenchymal proteomes of this model. In a cohort of presymptomatic mice both the cortex and hippocampus proteomes were mapped in male as well as female mice. In the four proteomes profound adaptations were identified, and previous findings of an early and severe pathology in Tg-SwDI female mice are reaffirmed on the molecular level. In addition, the effectiveness of two Carbonic Anhydrase Inhibitors (CAIs), Acetazolamide and Methazolamide, in preventing the observed molecular adaptations was evaluated. These repurposed drugs broadly prevented the proteome adaptations in the Tg-SwDI mice.
Project description:The Nrf2 transcription factor is a key player in the cellular stress response, which regulates the expression of important antioxidant enzymes and other cytoprotective proteins. We recently generated a novel transgenic mouse model to determine the function of Nrf2 in the skin. These mice show reduced number of apoptotic keratinocytes after UVB irradiation due to enhanced ROS detoxification. They also show enhanced tumorigenesis in the HPV8 tumor model.
Project description:BACKGROUND AND AIMS: Loss of epithelial cell homeostasis and apoptosis highly con-tribute to intestinal inflammation. While endoplasmic reticulum unfolded protein response (UPR) has been implicated in chronic intestinal inflammation, functional correlation between UPR-related C/EBP homologous protein (CHOP) expression and CHOP-mediated programming towards inflammation-related disease susceptibility remains unclear. In this study, we generated the new mouse model ChopIEC Tg/Tg to investigate consequences of intestinal epithelial cell (IEC)-specific CHOP overexpression. Transcriptional profiling of transgenic mice identified a set of CHOP-dependent target genes related to inflammatory and microbial defense program in the intestinal epithelium. Effect of CHOP overexpression in intestial epithelial cells was investigated on epithelial homeostasis using transgenic mice Disease-free mice do not show enhanced apoptotic signaling Intestinal epithelial cells were isolated from 12 week old females
Project description:Leukemic splenocytes from these commercial transgenic mice that developed fatal leukemia with massive splenomegaly were isolated at the time of the necropsy and subjected to gene expression profiling and phosphoprotein profiling in side by side comparison with CD22DE12-Tg BPL or CD22DE12_BCR-ABL double transgenic cells. Mouse leukemia cells were isolated from markedly enlarged spleens of CD22DE12-Tg (N=2), BCR-ABL-Tg (N=2), Eµ-MYC Tg mice (N=2) and Splenocytes from wildtype healthy C57BL/6 mice served as controls (N=4).
Project description:Microarray gene profiling of skin from PLA2G10-Tg mice in comparison with that from control mice yielded data for explaining the overall tendency of Tg skin to show hair follicle distortion and epidermal hyperplasia associated with hyperkeratosis in the absence of inflammation Pla2g10-Tg/+ mice and littermate controls (C57BL/6 background); 25-day old; skin; pooled from 4 mice for each genotype.
Project description:Comparitive gene expression in skin between mice maintained in microgravity (0g) and normogravity (1g) environment. Six male C57Bl/J10 mice were housed for 91 days in the specially designed \Mouse Drawer System\ in weightlessness aboard the International Space Station. Three wild-type mice (WT) and three transgenic mice overexpressing the osteogneic factor PTN/OSF1 under the control of the human bone specific ostecalcin promoter (Tg) were used in the experiment. During the 3-month stay on the ISS, 3 mice unfortunately died leaving 2 Tg and 1 WT. \MDS tissue sharing program\ allowed several teams to study various tissues from these mice. Our aim was to investigate the effect of such a long period of microgravity on skin physiology by morphological, biochemical and genomewide analyses by comparison to similar mice on ground. Gene expression in the skin of 3 space mice and of 3 ground mice was analyzed by microarray. As this unique experiment performed on 3 mice limits the power of statistical analyis, as the transgene PTN/OSF1 was not overexpressed in skin and as a pair wise Pearson's correlation rates between the individual levels of expressed transcripts in the WT and the Tg mice were not significantly different from each other in one experimental group (space or ground), data from the 3 mice were combined to compare results from the space an ground groups.