Molecular and metabolic effects of norUDCA in Abcb4 knockout mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE26547 | GEO | 2011/02/02
SECONDARY ACCESSION(S): PRJNA136627
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.
2011-08-01 | GSE26699 | GEO
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 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. ABCB4 locus microdeletions characterization vs reference sample (pool of six normal control DNAs)
2011-10-04 | E-GEOD-28676 | biostudies-arrayexpress
Project description:The renal clearance of perfluorooctanoic acid (PFOA) increased in Abcb4 null mice compared with wild type mice, especially in male Abcb4 null mice. We evaluated the expression changes of transporters in kidney of male Abcb4 null mice by using microarray to reveal the candidate transporters of PFOA.
2011-06-21 | GSE30084 | GEO
Project description:The renal clearance of perfluorooctanoic acid (PFOA) increased in Abcb4 null mice compared with wild type mice, especially in male Abcb4 null mice. We evaluated the expression changes of transporters in kidney of male Abcb4 null mice by using microarray to reveal the candidate transporters of PFOA. Male of Abcb4-null mice and wild-type mice (3 mice of 8 weeks old in each group) were sacrificed, collected their kidneys. Six independent experiments were performed.
2011-06-21 | E-GEOD-30084 | 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
Project description:The liver is the central organ critically regulating the balance of the metabolically potent yet toxic bile acids in the body. While genomic association studies have pointed to hepatic Sel1L – a critical component of mammalian Hrd1 ER-associated degradation (ERAD) machinery – as an influencer of serum bile acid levels, physiological relevance and mechanistic insights of ERAD in bile homeostasis remain unexplored. Using hepatocyte-specific Sel1L-deficient mouse models, we report that hepatic Sel1L-Hrd1 ERAD critically manages bile homeostasis in the body. Mice with hepatocyte-specific Sel1L developed intrahepatic cholestasis, with significant overload of bile acids in the liver and circulation under basal condition, and were hypersensitive to dietary bile acid challenge. By contrast, biliary bile acid and phosphatidylcholine levels were reduced, pointing to an export defect from hepatocytes. Unbiased proteomics analysis followed by biochemical assays revealed significant accumulation of the bile-stabilizing phosphatidylcholine exporter ATP-binding cassette 4 (Abcb4) in the ER of Sel1L-deficient livers, a gene associated with Progressive Familial Intrahepatic Cholestasis type III. Indeed, Abcb4 was a substrate of Sel1L-Hrd1 ERAD. Hence, hepatic Sel1L-Hrd1 ERAD maintains bile equilibrium via quality control of Abcb4 maturation in the ER.
2023-03-11 | PXD035243 | Pride