Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA340986 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4099650.fastq.gz | Fastqsanger.gz | |||
| SRR4099651.fastq.gz | Fastqsanger.gz | |||
| SRR4099652.fastq.gz | Fastqsanger.gz | |||
| SRR4099653.fastq.gz | Fastqsanger.gz | |||
| SRR4099654.fastq.gz | Fastqsanger.gz |
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Project description:Iron overload causes the generation of reactive oxygen species, which can lead to lasting damage to the liver and other organs. We studied the effects of iron deficiency and iron overload on the hepatic transcriptional and metabolomic profile in mouse models.
2018-02-13 | GSE86292 | GEO
Project description:Iron overload causes the generation of reactive oxygen species, which can lead to lasting damage to the liver and other organs. We studied the effects of iron deficiency and iron overload on the hepatic transcriptional and metabolomic profile in mouse models.
2018-02-13 | GSE86236 | GEO
Project description:Tissue iron (Fe) overload is a frequent pathologic finding in multiple disease states including non-alcoholic fatty liver disease (NAFLD), neurodegenerative disorders, cardiomyopathy, diabetes, and some forms of cancer. The role of iron, as a cause or consequence of disease progression and observed phenotypic manifestations, remains controversial. In addition, the impact of genetic variation on iron overload related phenotypes is unclear, and the identification of genetic modifiers is incomplete. Here, our aim was to characterize the genetic architecture of dietary iron overload and pathology using the Hybrid Mouse Diversity Panel (HMDP), a panel of over 100 genetically distinct mouse strains optimized for genome-wide association studies and systems genetics. Dietary iron overload was induced by feeding male mice (114 strains, 6-7 mice per strain on average) a high iron diet for six weeks, and then tissues were collected at 10-11 weeks of age. Liver metal levels and gene expression were measured by ICP-MS and RNASeq, and lipids were measured by colorimetric assays. FaST-LMM was used for genetic mapping, and Metascape, WGCNA, and Mergeomics were used for pathway, module, and key driver bioinformatics analyses. Mice on the high Fe diet accumulated Fe in the liver, with a 6.5-fold difference across strain means. The iron loaded diet also led to a spectrum of copper deficiency and anemia, with liver copper levels highly correlated with red blood cell count, hemoglobin, and hematocrit. Hepatic steatosis of various severity was observed histologically, with 52.5-fold variation in triglyceride (TG) levels across the strains. TG and Fe mapped most significantly to an overlapping locus on chromosome 7 that has not been previously associated with either trait. Based on network modeling, significant key drivers for both Fe and TG accumulation are involved in cholesterol biosynthesis and oxidative stress management. To make the full data set accessible and useable by others, we have made our data and analyses available on a resource website.
2023-08-11 | GSE230674 | GEO
Project description:Hereditary hemochromatosis and transfusional iron overload are frequent clinical conditions associated with progressive iron accumulation in parenchymal tissues leading to eventual organ failure. We have discovered a novel mechanism to reverse iron overload by pharmacological modulation of the divalent metal transporter-1 (DMT-1). DMT-1 mediates intracellular iron transport during the transferrin cycle and apical iron absorption in the duodenum. Additional functions in iron handling in the kidney and liver are less well understood. We show that the L- type calcium-channel blocker nifedipine increases DMT-1 mediated cellular iron transport 10-to 100-fold at concentrations between 1-100 uM. Mechanistically, nifedipine causes this effect by prolongation of the activity of DMT-1 to transport iron. We show that nifedipine mobilizes iron from the liver of mice with primary and secondary iron overload, and enhances urinary iron excretion. Modulation of DMT-1 function by L-type calcium-channel blockers emerges a novel pharmacological concept to treat iron overload disorders.<br> <br> In this experiment mice were subjected to dietary iron overload before being treated with nifedipine at 5 ug/g bodyweight, or mock treated with the same volume of solvent.
2007-03-01 | E-MEXP-982 | biostudies-arrayexpress
Project description:Genetic Model of iron deficiency in the Mouse Liver
| PRJNA341363 | ENA
Project description:Effects of Hfe-/- and dietary iron overload on gene expression in the liver and duodenum of mice
| PRJNA119943 | ENA
Project description:Homeostatic adaptation to systemic iron overload involves transcriptional induction of bone morphogenetic protein 6 (BMP6) in liver sinusoidal endothelial cells (LSECs). BMP6 is then secreted to activate signaling to the iron hormone hepcidin (Hamp) in neighboring hepatocytes. To explore the mechanism for iron sensing by LSECs, we generated TfrcTek-Cre mice with endothelial cell-specific ablation of transferrin receptor 1 (Tfr1). We also used wild type mice to characterize LSEC-specific molecular responses to iron by single cell transcriptomics. TfrcTek-Cre animals tend to have increased liver iron content compared to Tfrcfl/fl controls but do not exhibit blunted Bmp6 or Hamp mRNA expression. They respond to dietary iron challenges with Bmp6 and Hamp induction, yet sometimes to levels slightly lower relative to liver iron load. We noted that liver Bmp6 and Hamp mRNA levels significantly correlated with serum non-transferrin bound iron (NTBI) that emerged following dietary iron loading in both TfrcTek-Cre and Tfrcfl/fl mice. High dietary iron triggered more profound alterations in the LSEC transcriptome of Tfrcfl/fl mice compared to holo-transferrin injection. These culminated in robust induction of Bmp6 and other nuclear factor erythroid 2-related factor 2 (Nrf2) target genes, as well as Myc target genes involved in ribosomal biogenesis and protein synthesis. Taken together, our data suggest that during systemic iron overload, LSECs internalize NTBI, which promotes oxidative stress and thereby transcriptionally induces Bmp6 via Nrf2. The contribution of Tfr1 and transferrin-bound iron to Bmp6 induction is minimal.
2022-12-21 | GSE215324 | GEO
Project description:Iron is an essential trace element whose absorption is usually tightly regulated in the duodenum. HFE-related hereditary hemochromatosis (HH) is characterized by abnormally low expression of the iron-regulatory hormone, hepcidin, which results in increased iron absorption. The liver is crucial for iron homeostasis as it is the main production site of hepcidin. The aim of this study was to explore and compare the genome-wide transcriptome response to Hfe deficiency and dietary iron overload in murine liver and duodenum.
2009-09-05 | GSE17969 | GEO
Project description:Background & Aims: Although hepcidin expression was shown to be induced by the BMP signaling pathway, it is not yet known how iron regulates hepcidin and which of the BMP molecules is the endogenous regulator of iron homeostasis in vivo. We therefore assessed liver transcription profiles of mice fed an iron-deficient or an iron-enriched diet and looked for genes that were regulated similarly to hepcidin in that context. Methods: Genome-wide liver expression profiles of mice of the B6 and D2 genetic backgrounds subjected to iron-deficient, -balanced, or -enriched diets were obtained using Agilent Whole Genome microarrays. Real-time quantitative-PCR and western-blots were used to confirm microarray results and compare gene expression variations induced by secondary iron deficiency or iron overload with those consecutive to Smad4 or Hamp1-deficiency. Results: Among 1419 transcripts significantly modulated by the dietary iron content, four were regulated similarly to the hepcidin genes Hamp1 and Hamp2. They are coding for Bmp6, the regulator of Bmp/Smad signal transduction Smad7, the negative regulator of basic helix-loop-helix (bHLH) proteins Id1, and a protein with a bHLH domain, Atoh8. The iron overload developed by Smad4 and Hamp1-deficient mice also increased Bmp6 transcription. Body iron stores influence Smad1/5/8 phosphorylation and, as shown by analysis of mice with liver-specific disruption of Smad4, the binding partner for the receptor-activated Smads is necessary for activation of Smad7, Id1, and Atoh8 transcription by iron. Conclusions: Liver expression of Bmp6, Smad7, Id1, and Atoh8 is regulated by body iron stores and may participate in hepcidin regulation through the Bmp/Smad pathway. Keywords: response to dietary iron content
2008-07-07 | GSE10421 | GEO
Project description:Sex differences in liver gene expression are dictated by sex-differences in circulating growth hormone (GH) profiles. Presently, the pituitary hormone dependence of mouse liver gene expression was investigated on a global scale to discover sex-specific early GH response genes that might contribute to sex-specific regulation of downstream GH targets and to ascertain whether intrinsic sex-differences characterize hepatic responses to plasma GH stimulation. RNA expression analysis using 41,000-feature microarrays revealed two distinct classes of sex-specific mouse liver genes: genes subject to positive regulation (class-I) and genes subject to negative regulation by pituitary hormones (class-II). Genes activated or repressed in hypophysectomized (Hypox) mouse liver within 30-90min of GH pulse treatment at a physiological dose were identified as direct targets of GH action (early response genes). Intrinsic sex-differences in the GH responsiveness of a subset of these early response genes were observed. Notably, 45 male-specific genes, including five encoding transcriptional regulators that may mediate downstream sex-specific transcriptional responses, were rapidly induced by GH (within 30min) in Hypox male but not Hypox female mouse liver. The early GH response genes were enriched in 29 male-specific targets of the transcription factor Mef2, whose activation in hepatic stellate cells is associated with liver fibrosis leading to hepatocellular carcinoma, a male-predominant disease. Thus, the rapid activation by GH pulses of certain sex-specific genes is modulated by intrinsic sex-specific factors, which may be associated with prior hormone exposure (epigenetic mechanisms) or genetic factors that are pituitary-independent, and could contribute to sex-differences in predisposition to liver cancer or other hepatic pathophysiologies.
2010-01-27 | GSE17644 | GEO