Expression data from Hfe-deficient liver and duodenum in mouse strains with differing susceptibilities to iron loading
ABSTRACT: Hfe disruption in the mouse leads to experimental hemochromatosis by a mechanism which remains elusive. Evidence for at least five modifier genes has been obtained. These account for the higher iron load of Hfe-deficient D2 mice compared to B6 mice. Gene expression profling was used to clarify the mechanism of Hfe action and to identify potential modifier genes. Keywords: response to genetic modification Overall design: Liver and duodenum were obtained from wild-type and Hfe-deficient B6 and D2 mice (three mice per strain/genotype combination).
Project description:Hfe disruption in the mouse leads to experimental hemochromatosis by a mechanism which remains elusive. Evidence for at least five modifier genes has been obtained. These account for the higher iron load of Hfe-deficient D2 mice compared to B6 mice. Gene expression profling was used to clarify the mechanism of Hfe action and to identify potential modifier genes. Experiment Overall Design: Liver and duodenum were obtained from wild-type and Hfe-deficient B6 and D2 mice (three mice per strain/genotype combination).
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. Overall design: C57BL/6 male mice were used following the next scheme: 3 Hfe knockout mice and 2 wild type mice as their controls; 3 mice with dietary iron overload and 2 mice fed a standard diet as their controls. 2 tissues were analyzed from all the described mice, liver and duodenum. As an exception, the duodenum samples of only 2 Hfe knockout mice, instead of 3, were used. This makes a total of 19 samples: 10 liver samples and 9 duodenum samples.
Project description:Transcriptome changes were studied in the brain of 13 week male AKR mice with disruption of two iron regulatory genes, hemochromatosis Hfe and transferrin receptor 2 (Tfr2) compared to age and gender matched wildtype controls. The characterization of these mice is developed by Delima et al. 2012 (Delima, R. D., A. C. G. Chua, J. E. E. Tirnitz-Parker, E. K. Gan, K. D. Croft, R. M. Graham, J. K. Olynyk and D. Trinder (2012). Disruption of hemochromatosis protein and transferrin receptor 2 causes iron-induced liver injury in mice. Hepatology 56(2): 585-593.) Overall design: Male mice (n=4 per group) were maintained ad libitum on a standard diet containing approximately 0.02% iron. To maximize iron status, Hfe-/-xTfr2mut mice were switched to an iron-supplemented diet containing 2% carbonyl iron for three weeks prior to sacrifice at 13 weeks of age. Brain hemispheres were snap-frozen in liquid nitrogen and stored at -80C.
Project description:Inflammation influences iron balance in the whole organism. A common clinical manifestation of these changes is the anemia of chronic disease (ACD; also called anemia of inflammation). Inflammation reduces duodenal iron absorption and increases macrophage iron storage, resulting in low serum iron concentrations (hyposideremia). Despite the protection hyposideremia provides against proliferating microorganisms, this iron withholding reduces the iron available to developing red blood cells and eventually contributes to the development of anemia. Hepcidin antimicrobial peptide (Hamp) is a hepatic defensin-like peptide hormone that inhibits duodenal iron absorption and macrophage iron release. Hamp has antimicrobial activity and is part of the type II acute phase response. It is also thought to play a critical regulatory role in the sequestration of iron in the context of ACD. We report that mice with deficiencies in the hemochromatosis gene product, Hfe, mount a general inflammatory response, but lack appropriate Hamp expression and fail to develop hyposideremia. These data suggest a previously unidentified role for Hfe in innate immunity and ACD.
Project description:This dataset consists of whole brain samples from 10 B6 and 12 D2 mice, in order to assess the amount of strain-specific alternative splicing. This design consists of whole brain total RNA samples from 10 B6 and 12 D2 mice
Project description:We determined duodenal and liver gene response patterns in mice with primary (Hfe ?/? and C282Y homozygous mice) and secondary iron overload versus 129S6/SvEvTac wild type controls.
Project description:DBA/2J (D2) and C57BL/6J mice (B6) were infected intra-nasally with 2x10^3 FFU of influenza A H1N1 (PR8) virus. Lungs were collected from mock-infected controls or at day 1,2,3,4 post infection. Expression data were obtained from three independent experiments. We infected a highly susceptible mouse strain (D2) and a resistant strain (B6) with PR8 and performed a genome-wide expression analysis. We found genes expressed in lung epithelium that were specifically down-regulated in D2 mice, whereas a cluster of genes on chromosome 3 was only down-regulated in B6. In both mouse strains, chemokines, cytokines and interferon-response genes were up-regulated, indicating that the main innate immune defense pathways were activated. However, many immune response genes were up-regulated in D2 much stronger than in B6, and several immune response genes were exclusively regulated in D2. Thus, susceptible D2 mice showed a hyper-inflammatory response. This response is similar to infections with highly pathogenic influenza virus and may serve as a paradigm for a hyper-inflammatory host response to influenza A virus.
Project description:This dataset consists of whole brain samples from 10 B6 and 12 D2 mice, in order to assess the amount of strain-specific alternative splicing. Overall design: This design consists of whole brain total RNA samples from 10 B6 and 12 D2 mice
Project description:To gain insight into the host cell types, cellular and molecular pathways possibly involved in the differential permissiveness to pulmonary replication of M. tuberculosis, we carried out transcript profiling studies on M. tuberculosis-infected lungs from congenic and parental strains. We were particularly interested in two groups of transcripts. The first group consists of transcripts which expression in the lung is regulated in response to M. tuberculosis infection (global response to infection), and that is obtained by comparing transcripts profiles of infected vs. uninfected lungs. The second group of transcripts is associated with increased resistance to M. tuberculosis infection of B6 and D2.B6-Chr7 mice. That list consists in the overlap between the lists commonly expressed in response to infection between resistant B6 and D2.B6-Chr7 but that show a significant difference in modulation when compared to infected susceptible D2.<br><br> In these experiments, B6, D2 as well as the D2.B6-Chr19, and D2.B6-Chr7 congenic lines were infected with M. tuberculosis and lungs were harvested at day 30 and day 70, and RNA was prepared. Three independent RNA samples from each group were converted to labeled cDNAs and hybridized to Affymetrix oligonucleotides arrays (Mouse Genome 430 2.0 array). Hybridization results were analyzed with the Genesifter analysis program to characterize changes in gene expression.