Liver tissue from liver specific Vps33b knockout (Vps33bfl/fl-AlfpCre) and control (Vps33bfl/fl) mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Paul Gissen
PROVIDER: E-GEOD-83192 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Liver tissue from Vps33b liver ko (Vps33bfl/fl-AlfpCre) mice is a model of liver disease associated with ARC syndrome, an autosomal recessive inherited metabolic disorder cause by mutations in VPS33B or VIPAS39. ARC is a multisystem disorder, with liver and kidneys affected in particular. Defects in hepatocyte polarity have been identified. Affymetrix arrays were used to characterise the changes in the liver transcriptome when Vps33b is not expressed.
2016-06-10 | GSE83192 | GEO
Project description:We characterize the phenotype of mice in which the deletion of Lkb1 has been targeted in the liver. Lack of Lkb1 in the liver results in bile duct paucity leading to cholestasis. This phenotype is similar to that obtained upon inactivation of Notch signaling in the liver. We test the hypothesis of a functional overlap between the Lkb1 and Notch pathways by gene expression profiling of livers deficent in Lkb1 or in the Notch mediator RbpJκ. We used AlfpCre mice for liver-specific deletion of LKB1 that were crossed with a conditional knockout mouse model (LKB1 floxed mice). We used also AlfpCre mice for liver-specific inactivation of the Notch pathway. AlfpCre mice were crossed with the RbpJκ floxed mice. RNA was extracted from the liver of LKB1 KO mice (Lkb1Floxed, AlfpCre positive mice) and their wild-type counterpart (Lkb1Floxed, AlfpCre negative mice). RNA was also extracted from liver of RbpJK KO mice (RbpJK floxed, AlfpCre positive) and their wild type mice (RbpJK floxed, AlfpCe negative).
2015-12-08 | GSE75564 | GEO
Project description:We characterize the phenotype of mice in which the deletion of Lkb1 has been targeted in the liver. Lack of Lkb1 in the liver results in bile duct paucity leading to cholestasis. This phenotype is similar to that obtained upon inactivation of Notch signaling in the liver. We test the hypothesis of a functional overlap between the Lkb1 and Notch pathways by gene expression profiling of livers deficent in Lkb1 or in the Notch mediator RbpJκ. We used AlfpCre mice for liver-specific deletion of LKB1 that were crossed with a conditional knockout mouse model (LKB1 floxed mice). We used also AlfpCre mice for liver-specific inactivation of the Notch pathway. AlfpCre mice were crossed with the RbpJκ floxed mice. RNA was extracted from the liver of LKB1 KO mice (Lkb1Floxed, AlfpCre positive mice) and their wild-type counterpart (Lkb1Floxed, AlfpCre negative mice). RNA was also extracted from liver of RbpJK KO mice (RbpJK floxed, AlfpCre positive) and their wild type mice (RbpJK floxed, AlfpCe negative). 6 samples for the liver-specific deletion of LKB1 corresponding to 3 KO LKB1 (Cre positive) and 3 normal liver (Cre negative). 6 samples for the liver-specific inactivation of the Notch pathway corresponding to 3 KO RbpJk (Cre positive) and 3 normal liver (Cre negative).
2015-12-08 | E-GEOD-75564 | biostudies-arrayexpress
Project description:Scaffold proteins regulate intracellular MAP kinase signaling by providing critical spatial and temporal specificity. We have shown previously that the scaffold protein MEK1 partner (MP1) is localized to late endosomes by the adaptor protein p14. Using conditional gene disruption of p14 in livers of mice we analysed protein and transcript signatures in tissue samples. Further biological network analysis predicted that the differentially expressed transcripts and proteins are involved in cell cycle progression and regulation of cellular proliferation. Although some of the here identified signatures were previously linked to phospho-ERK activity, most of them were novel targets of late endosomal p14/MP1/MEK/ERK signaling module. Finally, the proliferation defect was confirmed in a chemically induced liver regeneration model in p14 liver knock-out mice. Conditional liver p14 KO mice were generated by mating p14 f/f mice with mice expressing Cre recombinase under control of Alb promoter and alpha-fetoprotein enhancer. The obtained p14 floxed/floxed;AlfpCre(p14 liver KO) mice were used in experiments as KO mice. To prevent the influence of AlfpCre transgene we used p14 +/+;AlfpCre mice as a control. All mice were derived in a C57BL/6 background and were six weeks old.
2011-02-01 | GSE24461 | GEO
Project description:Scaffold proteins regulate intracellular MAP kinase signaling by providing critical spatial and temporal specificity. We have shown previously that the scaffold protein MEK1 partner (MP1) is localized to late endosomes by the adaptor protein p14. Using conditional gene disruption of p14 in livers of mice we analysed protein and transcript signatures in tissue samples. Further biological network analysis predicted that the differentially expressed transcripts and proteins are involved in cell cycle progression and regulation of cellular proliferation. Although some of the here identified signatures were previously linked to phospho-ERK activity, most of them were novel targets of late endosomal p14/MP1/MEK/ERK signaling module. Finally, the proliferation defect was confirmed in a chemically induced liver regeneration model in p14 liver knock-out mice. Conditional liver p14 KO mice were generated by mating p14 f/f mice with mice expressing Cre recombinase under control of Alb promoter and alpha-fetoprotein enhancer. The obtained p14 floxed/floxed;AlfpCre(p14 liver KO) mice were used in experiments as KO mice. To prevent the influence of AlfpCre transgene we used p14 +/+;AlfpCre mice as a control. All mice were derived in a C57BL/6 background and were six weeks old. Expression profiles of KO mouse samples were compared to expression profiles of corresponding control mice and differentially expressed genes were identified.
2011-02-01 | E-GEOD-24461 | biostudies-arrayexpress
Project description:Background & Aims: Combined HCC/iCCA is a rare liver tumor type. We generated a transgenic mouse model (AlfpCre+-Trp53fl/fl/Alb-HBs+ tg mouse) which developed next to HCC combined HCC/iCCA (cHCC/iCCA). We compared bilineal differentiated liver carcinoma cell lines generated from primary liver tumors of AlfpCre+-Trp53fl/fl/Alb-HBs+ tg mice and transplanted them into C57BL/6J mice to monitor there agressiveness. We compared the geneexpression profile from those primary liver carcinoma cell lines with IFNγ treatment (pCCL-IFNγ) and without treatment (pCCL) with explanted primary carcinoma cell line (pCCL-ex). Results: Here we describe that elimination of HBs+ in pCCL by HBs/(Kb/S190-197)-specific CD8 T cells describes a potential immune escape mechanism for highly aggressive cHCC/iCCA-type liver carcinomas.
2023-05-23 | GSE215059 | GEO
Project description:Background and Aims: p53 can limit the self-renewal of stem cells from various tissues. Experimental evidence suggests that deletion of p53 can cooperate with other oncogenic events to induce aberrant self-renewal and transformation of progenitor cells. It is not known whether p53 deletion alone can lead to liver tumor formation. Methods: We used AlfpCre mice for liver-specific deletion of Trp53 in a conditional knockout mouse model to analyze liver carcinogenesis. Results: Here, we show that liver-specific deletion of p53 in mice consistently induces formation of liver carcinoma depicting bilineal differentiation. Freshly isolated p53-/- liver progenitor cells and hepatocytes exhibit chromosomal imbalances and an enhanced clonogenic capacity compared to p53-positive cells or p21-deficient cells. Primary cultures of hepatocytes and liver progenitor cells from p53-/- mice formed tumors with bilineal differentiation when transplanted into immuno-compromised mice. Together, these results indicate that loss of p53 alone is sufficient to induce primary liver cancer with bilineal differentiation originating from chromosomal instable cultured liver progenitor cells or hepatocytes. Conclusions: The study shows that p53-dependent checkpoints inhibit transformation of liver progenitor cells and hepatocytes involving p21-independent mechanisms. Liver tumors derived from Trp53 KO mice, liver tumors from DEN-treated wildtype mice, Trp53 KO liver and wildtype liver were isolated and RNA was extracted. Agilent-026655 Mouse 4x44K v2 arrays were used.
2011-12-29 | E-GEOD-34760 | biostudies-arrayexpress
Project description:Suppressor of cytokine signaling 3 (SOCS3) down-regulates several signaling pathways in multiple cell types, and previous data suggest that SOCS3 may shut off cytokine activation at the early stages of liver regeneration. We developed hepatocyte-specific Socs3 knockout (Socs3 h-KO) mice to directly study the role of SOCS3 during liver regeneration after 2/3 partial hepatectomy (PH). Socs3 h-KO mice demonstrate marked enhancement of DNA replication and liver weight restoration after 2/3 PH in comparison with littermate controls. Without SOCS3, signal transducer and activator of transcription 3 (STAT3) phosphorylation is prolonged, and activation of the mitogenic kinases extracellular signal-regulated kinase 1/2 (ERK1/2) is enhanced after PH. In vitro, we show that SOCS3 deficiency enhances hepatocyte proliferation in association with enhanced STAT3 and ERK activation after epidermal growth factor (EGF) or interleukin 6 (IL-6) stimulation. Microarray analyses show that SOCS3 modulates a distinct set of genes after PH, which fall into diverse physiologic categories. Using a model of chemical-induced carcinogenesis, we found that Socs3 h-KO mice develop hepatocellular carcinoma (HCC) at an accelerated rate. By acting on cytokines and multiple proliferative pathways, SOCS3 modulates both physiologic and neoplastic proliferative processes in the liver, and may act as a tumor suppressor. Experiment Overall Design: Hepatocyte-specific excision of the Socs3 gene was achieved by breeding Socs3 fl/fl mice with mice expressing the Cre recombinase transgene under control of the albumin promoter (Alb-Cre+), yielding Socs3 h-KO mice. Socs3 fl/fl, Alb-Cre- littermates were used as controls for all experiments, and are henceforth referred to as littermates. All mice (C57BL/6) were free of Helicobacter species, housed in a specific pathogen free facility with 12-h light/dark cycles with free access to standard food and water. 2/3 PH and sham operations were performed as previously described (15, 50) (n=3-6 mice per genotype per time point). Liver remnants were weighed after removal of necrotic stumps and sutures, and compared to post-operative body weight. For HCC experiments, a single i.p. injection of DEN (5mg/kg, Sigma) was performed 12-14 d after birth. For short time points, a single injection of DEN (100mg/kg) (31) was given to 4 wk old mice. At indicated time points, mice were sacrificed by CO2 inhalation. All animal studies were carried out under approved IACUC protocols at the University of Washington.
2008-06-16 | E-GEOD-9549 | biostudies-arrayexpress
Project description:Mouse IMCD3 cell lines knocked-down for VPS33B, VIPAR and PLOD3 are used as models of ARC syndrome, an autosomal recessive disorder cause by mutations in VPS33B or VIPAR. Previous work has shown that ARC syndrome causes epithelial cell polarisation defectes and mislocalisation of membrane proteins, so polarised IMCD3 cells were used as an experimental model. Affymetrix arrays were used to characterise the changes to the transcriptome when protein levels of VPS33B, VIPAR and PLOD3 are reduced. mouse IMCD-3 cell lines, 15 samples in total, three biological repeats of each of: wild type, control shRNA, VPS33B shRNA, VIPAR shRNA, PLOD3 shRNA
2016-05-13 | E-GEOD-81376 | biostudies-arrayexpress
Project description:Background and aims: P53 limits the self-renewal of stem cells from various tissue. A Loss of p53 in combination with other oncogenic events results in aberrant self-renewal and transformation of progenitor cells. Here, we investigated whether a loss of p53 as a single genetic lesion is sufficient to induce liver tumor formation. Methods: AlfpCre mice were crossed with Trp53 conditional knockout mice to achieve a liver-specific loss of Trp53. Results: The liver-specific loss of Trp53 results in liver tumor formation. A high percentage of the tumors showed a mixed differentiation of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Conclusion: The liver-specific deletion of Trp53 is sufficient to induce liver tumor formation.
2021-01-22 | GSE156252 | GEO