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Abcb4 liver expression profiling

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE26699 | GEO | 2011/08/01

SECONDARY ACCESSION(S): PRJNA136371

REPOSITORIES: GEO

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Project description:Molecular factors governing liver pathology in abcb4 (-/-) mice. Dr. Nakken, Karl Esten, Dr. Berge, Knut E., Dr. Knut J. Labori, StÃ¥le NygÃ¥rd, Dr. Terese Haaland , professor Morten G. RÃ¦der. 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.

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Abcb4 liver expression profiling

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