Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA284239 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:In rodent liver, a single injection of N-nitrosodiethylamine (DEN) followed by chronic treatment with the antiepileptic drug phenobarbital (PB) promotes the outgrowth of hepatocellular tumors with activating mutations in Ctnnb1, encoding the transcription factor β-catenin. We now studied long-term effects of PB treatment in livers of transgenic mice with hepatocyte-specific knockout (KO) of Apc, a negative regulator of β-catenin signaling. The number of Apc KO hepatocytes present in the liver decreased with age, indicative of a selective disadvantage of Apc KO cells in the absence of PB. Following liver tumor promotion by PB in Apc KO mice for 9 months, tumor burden was quantified and histological appearance, gene expression profiles, and activity of oncogenic signaling pathways of the tumors were analyzed. In Apc KO mice fed with PB, we observed an increased hepatic tumor volume fraction and tumor multiplicity, as compared to non-promoted animals. Tumors in the PB-treated Apc KO group were mostly eosinophilic hepatocellular adenoma with activated β-catenin, due to the deletion of Apc. These tumors exhibited striking phenotypic similarities to DEN-induced Ctnnb1-mutated tumors, regarding histological appearance and expression of marker proteins and mRNAs. A particular sub-population of tumors, Apc KO-driven basophilic hepatocellular carcinomas, exclusively appeared in the non-PB-treated group but was absent from PB-promoted livers. In conclusion, phenobarbital promotes the outgrowth of Apc-deficient, β-catenin-activated hepatocellular adenoma while simultaneously inhibiting the formation of a certain population of Apc-driven hepatocellular carcinoma.
2018-05-17 | GSE68969 | GEO
Project description:Co-chaperone protein CAR Cytoplasmic Retention Protein (CCRP) interacts with various nuclear receptors and determines their localization. However, there is limited information about in vivo role of CCRP especially in nuclear receptor-mediated gene regulation. We have generated CCRP global knockout (KO) mouse and have employed whole genome microarray analysis to reveal the role of CCRP in gene regulation in the mouse liver treated with phenobarbital (CAR activator) or non-treated. Male WT and KO mice were fasted for 24 h followed by the treatment with phenobarbital or vehicle PBS for 6h. Phenobarbital significantly induced or repressed 1302 and 2744 genes in WT and KO, respectively. Interestingly, cholesterol synthesizing genes were significantly up-regulated in KO even without treatment. Mice were fasted for 24 h followed by the intraperitoneally treatment with PBS or phenobarbital at dose of 100 mg/kg body weight for 6 h, or non-treatment.
2015-01-05 | E-GEOD-56557 | biostudies-arrayexpress
Project description:Transcriptomic profiling of liver of Ctnnb1-KO and WT mice after 12 weeks exposure to Phenobarbital (miRNA)
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Project description:Transcriptomic profiling of liver of Ctnnb1-KO and WT mice after 12 weeks exposure to Phenobarbital (mRNA)
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Project description:Co-chaperone protein CAR Cytoplasmic Retention Protein (CCRP) interacts with various nuclear receptors and determines their localization. However, there is limited information about in vivo role of CCRP especially in nuclear receptor-mediated gene regulation. We have generated CCRP global knockout (KO) mouse and have employed whole genome microarray analysis to reveal the role of CCRP in gene regulation in the mouse liver treated with phenobarbital (CAR activator) or non-treated. Male WT and KO mice were fasted for 24 h followed by the treatment with phenobarbital or vehicle PBS for 6h. Phenobarbital significantly induced or repressed 1302 and 2744 genes in WT and KO, respectively. Interestingly, cholesterol synthesizing genes were significantly up-regulated in KO even without treatment.
2015-01-05 | GSE56557 | GEO
Project description:Transcriptomic characterization of ABCD2 KO mice to fibrate treatment in liver tissue, 3 months of age ABCD2 KO and age-matched WT mice were administered fenofibrate (100 mg/kg/day) for 14 days.
2014-04-01 | E-MTAB-2006 | biostudies-arrayexpress
Project description:ApoE KO mice were treated with Mas receptor agonist AVE 0991 fo 16 weeks. At the age of 6 months mice were killed, the kidneys were dissected and the mitochondria were isolated by differential centrifugation. Next, 2DE electrophoresis was conduced. Healthy control (C57BL/6J mice), apoE KO and apoE KO treated with AVE 0991 were compared. Gel pieces containing protein spots of interest were destained, reduced, alkylated, digested with modified trypsin and analysed by LC-MS/MS method.
2016-05-09 | PXD000233 | Pride
Project description:cis-Apc+/Delta716/Smad4+/- mice spontaneously develop multiple invasive intestinal carcinomas due to loss of heterozygosity and manifest symptoms associated with cancer cachexia within four months of age. To investigate the role of the liver in cachexia pathophysiology, we compared the transcriptomes of cachexia and control mouse livers. We isolated total RNA from livers of four C57BL/6N mice and four cis-Apc+/Delta716/Smad4+/- mice. Total RNA samples were then employed to perform microarray analysis (Agilent SurePrint G3 Mouse GE 8x60K Microarray).
2023-08-04 | E-MTAB-11771 | biostudies-arrayexpress
Project description:Liver cancer susceptibility varies between strains of experimental animal models due to multiple genetic and epigenetic factors. We used DNase I hypersensitivity mapping and transcriptomic profiling to investigate cis-regulatory element and transcriptional perturbations associated with the early stages of phenobarbital (PB)-mediated liver tumor promotion in susceptible versus resistant mouse strains (B6C3F1 versus C57BL/6).
2019-10-07 | GSE131344 | GEO
Project description:Age-related decline in brain endothelial cell (BEC) function critically contributes to cerebrovascular and neurodegenerative disease. Comprehensive atlases of the BEC transcriptome have become available but results from proteomic profiling are lacking. To gain insights into endothelial pathways affected by aging, we developed a magnetic-activated cell sorting (MACS)-based mouse BEC enrichment protocol compatible with high-resolution mass-spectrometry based proteomics. In this experiment, first we have compared MACS sorted BECs across multiple time points between 3 and 18 months of age. Using unsupervised cluster analysis, we found a segregation of age-related protein dynamics with biological functions including a downregulation of vesicle-mediated transport. Our approach uncovered changes not picked up by transcriptomic studies such as accumulation of vesicle cargo and receptor ligands including Apoe. Therefor in our next proteomics experiment we compared BECs from 3-months-old Apoe-KO and WT mice and found 111 and 103 proteins to be up- and downregulated, respectively. Comparing the BEC proteomic signature of young Apoe-KO mice with the signature of aged (18-months-old) WT mice we found a positive correlation suggesting an accelerating effect of Apoe deficiency on BEC aging.
2024-02-15 | PXD044996 | Pride