Expression data from P0 forebrain of wild-type and Elavl3/Elavl4 double knockout mice.
Ontology highlight
ABSTRACT: Neuronal Elavl-like (nElavl) RNA binding proteins have three paralogs (Elavl2, Elavl3 and Elavl4) in the mouse genome. This family of RNABPs have been implicated in a variety of post-transcriptional RNA processing mechanisms, including regulation of mRNA stability, alternative splicing, and translational regulation. In this study, using mouse exon arrays, we identify significant differences (p<0.01) in 119 transcripts between wild-type and Elavl3/Elavl4 double knockout forebrain tissue at postnatal day 0. A total of 10 samples were analyzed. These samples consisted of 5 littermate pairs of wild-type and Elavl3/Elavl4 double knockout mice.
Project description:Rett syndrome (RTT) is a neurodevelopmental disorder characterized by developmental regression around 6-18 months after birth, followed by a lifetime of intellectual disability, stereotyped behaviors, and motor deficits. RTT is caused by mutations in MeCP2, a methyl-CpG binding protein that was traditionally believed to repress gene expression. Gene expression studies of individual brain regions, however, have revealed that MeCP2 loss-of-function leads to the subtle activation and repression of its gene targets. However, these results may be confounded by the extensive neuronal cell heterogeneity inherent in these brain structures. To minimalize this issue of heterogeneity, we assessed whether Mecp2-null mice exhibited alterations in gene expression patterns in the striatum, a brain nucleus with relatively homogenous neuronal types and is highly relevant to the motor deficits observed in RTT. Despite the homogeneity of the tissue, the fold-change of the 127 differentially expressed genes we identified remained low with a mean change consistent with other studies. However, many of those genes differentially expressed in the striatum have not been previously identified in gene expression analyses of other brain regions. This suggests therefore that the differential expression of genes following loss of MeCP2 occurs in a tissue, or cell-type specific manner and thus MeCP2 function should be understood in a cellular context. In initiating this study, we reasoned that reducing the number of cell types in a microarray experiment may reveal transcriptional changes that are masked in a whole tissue analysis. We therefore focused on tissues more homogeneous in regards to the diversity of neuronal cell types they contain in order to discern gene expression changes in the absence of MeCP2. We chose to isolate the striatum, a tissue composed predominantly of GABAergic medium spiny neurons (MSNs). The striatum was resected from five symptomatic Mecp2-null (KO) male mice bearing the Bird allele and five wild-type (WT) littermates in a C57BL/6 background. We also isolated liver from the same individuals to serve as a non-neuronal control. RNA was isolated from these tissues, converted to cDNA, and hybridized to a single-channel Affymetrix GeneChip Mouse Exon 1.0 ST array for a total of 20 individual arrays.
Project description:Myeloid derived suppressor cells (MDSCs) are an immunosuppressive population of immature myeloid cells found in advanced stage cancer patients and mouse tumor models. To identify potential genes playing essential role in MDSC biology, we have conducted microarray analysis of gene expression in MDSCs from esophageal tumor-bearing mice, compared to immature myeloid cells from healthy littermate control mice. In this dataset, we include the expression data obtained from sorted splenic CD11b+Gr1+ cells from tumor-bearing L2-Cre;p120f/f mice, compared to healthy littermate controls. Using these data, we have identified 964 genes showing differential expression between the two groups. Among these was the Cd38 gene, which was among the genes most upregulated in MDSCs from tumor-bearing mice. 9 total samples were analyzed: 6 sample from experimental tumor-bearing mice and three pooled samples from control mice. Gene expression difference was determined by univariate test (two-sample t-test) with multivariate permutation test (10,000 random permutations). A cut-off p-value of less than 0.001 and minimum 2-fold expression change were used to identify genes with significant expression differences between the two groups.
Project description:Myeloid derived suppressor cells (MDSCs) are an immunosuppressive population of immature myeloid cells found in advanced stage cancer patients and mouse tumor models. We have identified Cd38 gene as potentially playing an essential role in MDSC biology. To determine the diffences between CD38high and CD38 low MDSCs from tumor-bearing mice, we have conducted this microarray. In this dataset, we include the expression data obtained from sorted splenic CD38high CD11b+Gr1+ cells from tumor-bearing L2-Cre;p120f/f mice, compared to CD38low CD11b+Gr1+ cells from the same mice. Using these data, we have detected differential expression of 498 genes . The Nos2 gene was among the genes most upregulated in CD38high MDSCs. 8 total samples were analyzed: 3 pairs of CD38high and CD38 low MDSCs (coming from individual mice), as well a pair of CD38high and CD38low pulled MSDCs (splenocytes from 3 mice were pulled together for sorting to increase yields). Gene expression difference was determined by univariate test (two-sample t-test) with multivariate permutation test (10,000 random permutations). A cut-off p-value of less than 0.001 and minimum 2-fold expression change were used to identify genes with significant expression differences between the two groups.
Project description:We sought to identify genes that are differentially regulated in CD11b+Gr1+ cells after tumor challenging. Mice were challenged with LLC-RFP cells (5×10^6 cells, subcutaneous injection) for 9 days. Single cell suspensions were prepared from lungs of both tumor challenged and control wild type mice and stained with antibodies against CD11b and Gr1. Approximately 1×10^5 CD11b+GR1+ myeloid progenitor cells were sorted by FACS (Aria II, BD Bioscience). Total RNA was extracted from the sorted cells for microarray analysis. In this dataset, we include the expression data of CD11b+Gr1+ cells obtained from both control wild type and tumor challenged mice. These data were used to obtain 22 genes that are upregulated in response to tumor challenging. We analyzed 3 samples from control mice and 2 samples tumor challenged mice. The mean values of the groups were used in the analysis. Genes that were upregulated >2 fold were sorted out and generate the table in the Matrix datasheet.
Project description:Transgenic mice expressing a truncated form of Zmiz1 in the skin develop spontaneous keratoacanthomas. In this experiment, a Cre-inducible transgene expressing a truncated form of Zmiz1 was introduced into mice. Activation of the transgene in these mice was achieved by breeding to K14-Cre transgenic animals. Double transgenic mice formed spontaenous keratoacanthomas with short latency. In this experiment, we generated gene expression profiles for five Zmiz1-induced keratoacanthomas and six normal skin samples.
Project description:Exposure to inflammatory cytokines driven by bystander cytokines can have profound effects on the function of memory CD8 T cells. Here we transferred a 1-5X10^4 of P14 TCR-tg T cells (specific for gp33-41 of LCMV) on day -1 followed by infection with 2X10^5 PFU of LCMV Armstrong ip to generate memory P14 populations. Mice were rested for >50 days before further challenge. Mice containing memory P14 populations were either mock-infected with saline, infected with 2X10^6 Pichinde Virus ip (no cross-reactivity wtih LCMV gp33-41) or infected with 2X10^6 Pichinde Virus ip together with daily injections of 200 micrograms of anti-CD122 antibody (clone TM-b1). On day 4 following indicated treatments P14s were flow sorted and RNA was extracted from 1X10^6 cells using an RNeasy kit (Qiagen). Each group had 3 biological replicates. Transcriptomes were compared by DAVID analysis (p<0.01, Fold-Change > 1.5) 3 biological replicates per group. Groups included P14 from mock-infected mice, P14 from Pichinde virus infected mice and P14 from Pichinde virus and anti-cd122 treated mice.
Project description:To characterize gene expression in Gata6 positive epidermal cells we analyzed a Gata6 reporter mouse in which the endogenous Gata6 promoter drives expression of mTomato. We performed flow cytometry followed by transcriptome analysis. We compared four subpopulations of telogen epidermal cells: Gata6+/Itga6+ cells, Gata6+/itga6- cells, CD34+/Itga6+ cells (which are Gata6-) and all remaining Itga6+ cells (Gata6-/CD34-). The RNA was isolated from age and sex matched mice. We compared four subpopulations of telogen epidermal cells: Gata6+/Itga6+ cells, Gata6+/itga6- cells, CD34+/Itga6+ cells (which are Gata6-) and all remaining Itga6+ cells (Gata6-/CD34-). The RNA was isolated from age and sex matched mice. Three biological replicates for each cell population were analyzed
Project description:In adult K14ÎNLef1 mouse, the overexpression of âNLef1, a B-catenin dominat negative, in basal keratinocytes leads to the conversion of hair follicles into multilayered epithelial cysts and ectopic sebaceous gland. To uncover in vivo changes in gene expression associated to âNLef1 activity, we compared the expression profiles of unfractionated keratinocytes in wild type and K14ÎNLef1 transgenic mice. Cells were collected from 9.5 week old mice, when the hair follicle are in the resting (telogen) phase of the hair growth cycle. At this stage the âNLef1 phenotype is not yet evident enabling us to detect early molecular events. We compared the expression profiles of unfractionated keratinocytes in wild type and K14ÎNLef1 transgenic 9.5 week old mice. Three biological replicates for each cell population were analyzed.
Project description:There are multiple stem cells in adult mammalian epidermis, but the mechanisms controlling lineage specification are poorly understood. To identify gene expression signatures of the three major epidermal differentiation compartments we micro-dissected individual SG, IFE and HF from adult epidermis. The RNA was isolated from age and sex matched wild-type mice and performed transcriptome analysis with Affymetrix Exon microarrays We micro-dissected individual interfollicular epidermis (IFE), hair follicle (HF) and sebaceous gland (SG) from adult tail epidermis. The RNA was isolated from age and sex matched wild-type mice. Three biological replicates for each epidermal differentiation compartment were analyzed.