Whole-genome profiling of the liver transcriptome in Trpm6 gene deficient mice and control littermates.
Ontology highlight
ABSTRACT: To attain deeper insight into metabolic alterations in Trpm6 gene deficient mice we used microarrays for profiling of hepatic transcripts of Trpm6 ko and control mice. We identified a set of gene networks up- or down-regulated in the liver of Trpm6 gene deficient mice.
Project description:To attain deeper insight into metabolic alterations in Trpm7 gene deficient mice we used microarrays for profiling of transcripts in villi of Trpm7 ko and control mice. We identified a set of gene networks up- or down-regulated in villi of Trpm7 gene deficient mice.
Project description:TAZ-deficient mice have the abnormalities in the lung development. We expect the comparison of the gene expression profiles of TAZ-deficient and wild-type lungs would reveal the underlying mechanisms. Keywords: genetic modification
Project description:The transient receptor potential melastatin type 6 (TRPM6) is a divalent cation channel pivotal for gatekeeping Mg2+ balance. To study the role of TRPM6 in the intestine, we generated mice lacking intestinal TRPM6 (Vill1-TRPM6-/-). In this study, the distal colon of Vill1-TRPM6-/- mice and of the control mice (TRPM6fl/fl) was subjected to RNA sequencing.
Project description:Transcriptional profiling of E14 Dlk+ cells derived from Matrix metalloproteinase (MMP)-14 deficient (KO) mice comparing those from littermate wild-type (WT) mice. RNA samples were extrated from FACS-sorted Dlk+CD45-CD71-Ter119- cells derived from E14.5 livers. Transcriptional profiling of postnatal day (P)1 livers derived from MMP-14 deficient (KO) mice comparing those from littermate wild-type (WT) mice. RNA samples were extrated from whole livers derived from P1 mice.
Project description:TAZ-deficient mice have the abnormalities in the lung development. We expect the comparison of the gene expression profiles of TAZ-deficient and wild-type lungs would reveal the underlying mechanisms. Experiment Overall Design: Four total RNA samples from E15.5 lungs were mixed for each group.
Project description:Hyaluronan receptor LYVE-1 is expressed by liver sinusoidal endothelial cells (LSEC), lymphatic endothelial cells and specialized macrophages. Besides binding hyaluronan, LYVE-1 mediates adhesion of leukocytes and cancer cells to endothelial cells. Here, we analyzed the impact of LYVE-1 on physiological liver functions and metastasis. Mice with deficiency of Lyve-1 (Lyve-1 KO) were analyzed using histology, immunofluorescence, RNA sequencing, plasma proteomics and flow cytometry. Liver metastasis was studied by intrasplenic/intravenous injection of melanoma (B16F10luc2, WT31) or colorectal carcinoma (MC38) cell lines. Results: Hepatic architecture, liver size, endothelial differentiation and angiocrine functions were unaltered in Lyve-1 KO mice. Hyaluronan plasma levels were significantly increased in Lyve-1-KO mice; besides, plasma proteomics revealed increased carbonic anhydrase-2 and decreased FXIIIA, potential modulators of metastatis. Furthermore, gene expression analysis of LSEC indicated regulation of immunological pathways. Therefore, liver metastasis of a highly and of a weekly immunogenic tumor, i.e. melanoma and colorectal carcinoma (CRC), was analyzed in Lyve-1 KO mice. Hepatic metastasis of B16F10 luc2 and WT31 melanoma cells, but not MC38 CRC cells, was significantly reduced in Lyve-1 KO mice. While short-term adhesion assays with B16F10 luc2 cells in vivo did not show differences between Lyve-1 KO and wild-type mice, increased numbers of resident hepatic CD4+, CD8+ and regulatory T cells were detected in Lyve-1 KO livers. In addition, iron deposition was detected in F4/80+ liver macrophages known to exert pro-inflammatory effects. Conclusions: LYVE-1 deficiency controlled hepatic metastasis in a tumor cell-specific manner reducing hepatic metastasis of melanoma, but not CRC. Anti-tumorigenic effects are likely due to enhancement of the resident hepatic immune microenvironment.
Project description:Transcriptional profiling of E18.5 livers derived from Wnt5a-deficient (KO) mice compared to those from littermate wild-type (WT) mice. RNA samples were extracted from whole livers derived from E18.5 fetuses. Two-condition experiment: Wnt5a KO vs. WT whole livers. Total RNA samples were extracted from E18.5 whole livers. KO and WT samples were a mixture of RNA solutions derived from two Wnt5a KO livers and two WT livers, respectively.
Project description:Activation of protein kinase C epsilon (PKCε) in the liver has been widely associated with hepatic insulin resistance. PKCε is proposed to inhibit insulin signalling through phosphorylation of the insulin receptor. We have tested this directly by breeding PKCε floxed mice with mice expressing Cre recombinase under the control of the cytomegalovirus, albumin or adiponectin promoters to generate global, liver- and adipose tissue-specific PKCε knockout (KO) mice. Global deletion of PKCε recapitulated the benefits for diet-induced glucose intolerance that we previously described using conventional PKCε KO mice. However, we did not detect PKCε-dependent alterations in hepatic insulin receptor phosphorylation. Furthermore, liver-specific KO mice were not protected against diet-induced glucose intolerance or insulin resistance determined by euglycemic clamp. In contrast, adipose tissue-specific KO mice exhibited improved glucose tolerance and mildly increased hepatic triglyceride storage, but no change in liver insulin sensitivity. Phosphoproteomic analysis of insulin signalling in PKCε KO adipocytes revealed no defect in the canonical INSR/AKT/mTOR pathways. However, PKCε KO resulted in changes in phosphorylation of several proteins associated with the endosome and cell junctions suggesting regulation in secretory pathways and a potential role of PKCε in endocrine function. Indeed, RNA-seq analysis revealed adipose-tissue PKCε-dependent changes in the hepatic expression of several genes linked to glucose homeostasis and hepatic lipid metabolism. The primary effect of PKCε on glucose homeostasis is therefore not exerted directly in the liver as currently assumed. However, PKCε in adipose tissue modulates glucose tolerance and is involved in crosstalk with the liver that affects gene expression and lipid accumulation.