Abcb4 liver expression profiling
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE26699 | GEO | 2011/08/01
SECONDARY ACCESSION(S): PRJNA136371
REPOSITORIES: GEO
Similar Datasets
Project description:The multidrug resistance gene 2 (Mdr2 or Abcb4) encodes a P-glycoprotein (Pgp) - a phospholipid flippase - that is the murine orthologue of the MDR3 gene in humans. The MDR2 protein is principally expressed in the bile canalicular membrane of the liver. A homozygous disruption of Abcb4 causes absence of phospholipids from bile. This phospholipid deficiency results in liver injury. The Balb-Abcb4-/- mouse strain has been generated by introgressing the Abcb4 knockout from the fibrosis-resistant FVB/NJ (FVB.129P2-Abcb4tm1Bor/J) strain into the susceptible BALB/cJ background, by backcrossing FVB- Abcb4-/- mice in to fibrosis-susceptible BALB/cJ mice for 10 generations. cDNA expression profiling of mRNA from liver of four single male mutant mice against a pool of RNA from four wild type controls (n=8). For each mutant animal two technical replicates were performed including a dye swap experiment.
2011-07-31 | E-GEOD-26699 | biostudies-arrayexpress
Project description:The Th2 cytokine IL-13 has been described to be involved in biliary epithelial injury and liver fibrosis in patients as well as in animal models. IL-13 was found to reduce tight junction-associated barrier function of bile ducts, to promote cholangiocyte hyperplasia, and thus causing biliary epithelial injury. We generated Abcb4-/-- and IL-13-/- double-knockout mice on fibrosis susceptible genetic background BALB/c. Molecular and cellular mechanisms of hepatic and ileal pathology were investigated by mRNA microarray. Depletion of IL-13 in Abcb4-/--mice resulted in a tenfold decrease of total serum bile acid concentrations at the age of 8 weeks and lead to a recovery of intrahepatic bile duct integrity. The decrease of serum bile acid in 8 week old mice went along with relative enhancement of bile acid excretion and normalization of the composition of fecal bile excretion, correction of fecal microbiome, and improved ileal integrity. Liver integrity, measured by serum ALT, was ameliorated in younger mice and strongly correlated with the concentration of serum bile acids. 52 weeks old Abcb4-/-IL-13-/--mice exhibited significantly reduced hepatic fibrosis.
2020-11-02 | GSE90995 | GEO
Project description:Molecular factors governing liver pathology in abcb4 (-/-) mice. Dr. Nakken, Karl Esten, Dr. Berge, Knut E., Dr. Knut J. Labori, Ståle Nygård, Dr. Terese Haaland , professor Morten G. Ræder. Institute for Experimental Medical Research and Department of Pathology, Ulleval University Hospital, Oslo, Norway and Institute for Medical Genetics, National Hospital, Oslo, Norway; E-mail: k.e.nakken@medisin.uio.no. Background and Aims: Abcb4 (mdr2) (-/-) mice secrete phosphatidylcholine-free bile and develop chronic cholangitis. This study aims at identifying differentially transcribed genes that govern liver pathology during this disease. Methods: Hepatic gene transcription was measured in 3, 6, 9 and 20 week old abcb4 (-/-) mice (FVB.129P2-abcb4tm1Bor/J) using cDNA microarrays; FVB/NJ abcb4 (+/+) mice serving as controls. Altered gene transcriptions were verified by real-time polymerase chain reaction. Attention focused on genes coding for chemokines and cytokines of potential pathogenic importance and on matrix housekeeping genes, growth factors and genes regulating wound healing, epithelial morphogenesis and tissue development. Disease phenotype was characterized by histopathology scoring. Results: Transcription of serpina3 genes showed early downregulation. Genes exhibiting upregulated transcription included: Cxcl10, Ccl2, Ccl20, Ctgf, Elf3, Lgals3, Mmp12, Mmp15, Spp1, Loxl2, Pdgfa, Pdgfrb, Sparc, Tgfbi, Tgfbr2. Conclusions: During early phases of chronic cholangitis in abcb4 (-/-) mice, hepatic downregulation of serpina3 genes and enhanced transcription of genes sustaining inflammatory processes contribute to fashioning the portal tract pathology. Later, enhanced transcription of genes governing tissue repair consolidate the portal tract pathology. Experiment Overall Design: A time-series where 5 male mice were sacrificed at time-points 3,6,9 and 20 weeks, both sick knockouts and healthy controls. Including one dye-swap there were a total of 6 arrays at each time-point.
2008-06-13 | E-GEOD-4603 | biostudies-arrayexpress
Project description:Molecular factors governing liver pathology in abcb4 (-/-) mice. Dr. Nakken, Karl Esten, Dr. Berge, Knut E., Dr. Knut J. Labori, Ståle Nygård, Dr. Terese Haaland , professor Morten G. Ræder. Institute for Experimental Medical Research and Department of Pathology, Ulleval University Hospital, Oslo, Norway and Institute for Medical Genetics, National Hospital, Oslo, Norway; E-mail: k.e.nakken@medisin.uio.no. Background and Aims: Abcb4 (mdr2) (-/-) mice secrete phosphatidylcholine-free bile and develop chronic cholangitis. This study aims at identifying differentially transcribed genes that govern liver pathology during this disease. Methods: Hepatic gene transcription was measured in 3, 6, 9 and 20 week old abcb4 (-/-) mice (FVB.129P2-abcb4tm1Bor/J) using cDNA microarrays; FVB/NJ abcb4 (+/+) mice serving as controls. Altered gene transcriptions were verified by real-time polymerase chain reaction. Attention focused on genes coding for chemokines and cytokines of potential pathogenic importance and on matrix housekeeping genes, growth factors and genes regulating wound healing, epithelial morphogenesis and tissue development. Disease phenotype was characterized by histopathology scoring. Results: Transcription of serpina3 genes showed early downregulation. Genes exhibiting upregulated transcription included: Cxcl10, Ccl2, Ccl20, Ctgf, Elf3, Lgals3, Mmp12, Mmp15, Spp1, Loxl2, Pdgfa, Pdgfrb, Sparc, Tgfbi, Tgfbr2. Conclusions: During early phases of chronic cholangitis in abcb4 (-/-) mice, hepatic downregulation of serpina3 genes and enhanced transcription of genes sustaining inflammatory processes contribute to fashioning the portal tract pathology. Later, enhanced transcription of genes governing tissue repair consolidate the portal tract pathology. Keywords: Disease state analysis, time course
2007-04-01 | GSE4603 | GEO
Project description:To identify (i) target genes relevant for the disease development (WT vs. Abcb4-/- mice) and (ii) to gain insights into mechanisms leading to the reversal of chronic cholestatic liver injury in Abcb4-/- mice treated with the side-chain modified bile acid "norUDCA" (Abcb4-/- mice vs. norUDCA treated Abcb4-/- mice).
2011-02-02 | GSE26547 | GEO
Project description:Growth hormone (GH) resistance has been associated with liver cirrhosis in humans but its contribution to the disease remains controversial. In order to elucidate whether GH resistance plays a causal role in the establishment and development of liver fibrosis, or rather represents a major consequence thereof, we challenged mice lacking the Growth hormone receptor gene (Ghr-/-, a model for GH resistance) by crossing them with Mdr2 knockout mice (Mdr2-/-), a mouse model of inflammatory cholestasis and liver fibrosis. Ghr-/-;Mdr2-/- mice showed elevated serum markers associated with liver damage and cholestasis, extensive bile duct proliferation and increased collagen deposition relative to Mdr2 -/- mice, thus suggesting a more severe liver fibrosis phenotype. Additionally, Ghr-/-;Mdr2-/- mice had a pronounced down-regulation of hepato-protective genes Hnf6, Egfr and Igf-1, and significantly increased levels of ROS and apoptosis in hepatocytes, compared to control mice. Moreover, single knockout mice (Ghr-/-) fed with a diet containing 1% cholic acid displayed an increase in hepatocyte ROS production, hepatocyte apoptosis and bile infarcts compared to their wildtype littermates, indicating that loss of Ghr renders hepatocytes more susceptible to toxic bile acid accumulation. Surprisingly, and despite their severe fibrotic phenotype, Ghr-/-;Mdr2-/- mice displayed a significant decrease in tumour incidence compared to Mdr2-/- mice, indicating that loss of Ghr signaling may slow the progression from fibrosis/cirrhosis to cancer in the liver.
2020-06-20 | GSE58908 | GEO
Project description:Mdr2 is the transporter of phosphatidylcholine, which is an essential component of bile. Deficiency of mdr2 causes hepatic inflammation, liver fibrosis and hepatocellular carcinoma. Mdr2-/- MEFs show increased proliferation, spontaneous transformation and tumorigenesis. We used microarray to obtain genome-wide profiling of gene expression underlying the changes in mdr2-/- MEFs.
2015-09-02 | GSE72615 | GEO
Project description:Mdr2 is the transporter of phosphatidylcholine, which is an essential component of bile. Deficiency of mdr2 causes hepatic inflammation, liver fibrosis and hepatocellular carcinoma. Mdr2-/- MEFs show increased proliferation, spontaneous transformation and tumorigenesis. We used microarray to obtain genome-wide profiling of gene expression underlying the changes in mdr2-/- MEFs. MEFs derived from wt and mdr2-/- littermate embyos were subjected to passage according to 3T3 protocols. RNA was extracted from cells on passage 40 and hybridized on Affymetrix microarrays.
2015-09-02 | E-GEOD-72615 | biostudies-arrayexpress
Project description:Background and aims: Signal transducer and activator of transcription 3 (Stat3) is the main mediator of interleukin-6 type cytokine signaling required for hepatocyte proliferation and hepatoprotection but its role in sclerosing cholangitis and other cholestatic liver diseases remains unresolved. Methods: We investigated the role of Stat3 in inflammation-induced cholestatic liver injury and used mice lacking the multidrug resistance gene 2 (mdr2-/-) as a model for SC. Results: We demonstrate that conditional inactivation of stat3 in hepatocytes and cholangiocytes (stat3 delta hc) of mdr2-/- mice strongly aggravated bile acid-induced liver injury and fibrosis. A similar phenotype was observed in mdr2-/- mice lacking IL-6 production. Biochemical and molecular characterization suggested that Stat3 exerts hepatoprotective functions in both, hepatocytes and cholangiocytes. Loss of Stat3 in cholangiocytes led to increased expression of TNFα which might reduce the barrier function of bile ducts. Loss of Stat3 in hepatocytes led to upregulation of bile acid biosynthesis genes and downregulation of hepatoprotective epidermal growth factor receptor and insulin-like growth factor 1 signaling pathways. Consistently, stat3deltahc mice were more sensitive to cholic acid-induced liver damage than control mice. Conclusions: Our data suggest that Stat3 prevents cholestasis and liver damage in sclerosing cholangitis via regulation of pivotal functions in hepatocytes and cholangiocytes. Affymetrix microarray analyses was performed to identify metabolic and molecular pathways in stat3Dhc mdr2-/- mice that lead to cholestasis and bile acid-induced liver injury. To avoid false positive results that are due to differential cellular composition, we defined the onset of fibrosis and expression of fibrogenic factors in stat3Dhc mdr2-/- mice.
2010-10-20 | E-GEOD-18759 | biostudies-arrayexpress
Project description:To allow acute characterization of ABCB4 locus constitutional deletion in two patients with cholelithiasis/cholestasis, an Agilent 2X400 array CGH was used. Goal was to obtain genomic rearrangements fine characterization in order to describe ABCB4 constitutional deletions.
2011-10-05 | GSE28676 | GEO