Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse mutant abcb4 (-/-)

ABSTRACT: 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.

ORGANISM(S): Mus musculus

SUBMITTER: Esten Nakken

PROVIDER: E-GEOD-4603 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Multiple inflammatory-, tissue remodelling- and fibrosis genes are differentially transcribed in the livers of Abcb4 (-/ - ) mice harbouring chronic cholangitis.

Nakken Karl Esten KE Nygård Ståle S Haaland Terese T Berge Knut Erik KE Arnkvaern Kristin K Ødegaard Annlaug A Labori Knut Jørgen KJ Raeder Morten G MG

Scandinavian journal of gastroenterology 20071001 10

<h4>Objective</h4>Abcb4 (-/-) mice secrete phosphatidylcholine-free, cytotoxic bile and develop chronic cholangitis. The aim of this study was to identify differentially transcribed genes whose products contribute to the liver tissue pathology during this disease.<h4>Material and methods</h4>Hepatic gene transcription was measured in 3-, 6-, 9- and 20-week-old Abcb4 (-/-) mice (FVB.129P2-abcb4(tm1Bor)/J) using cDNA microarrays, with FVB/NJ Abcb4 (+/+) mice serving as controls. Focus was on infla ...[more]

PMID: 17852852

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Dataset Information

Transcription profiling of mouse mutant abcb4 (-/-)

Publications

Multiple inflammatory-, tissue remodelling- and fibrosis genes are differentially transcribed in the livers of Abcb4 (-/ - ) mice harbouring chronic cholangitis.

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