Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA231176 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Development of LNA gapmers, antisense oligonucleotides used for efficient inhibition of target RNA expression, is limited by non-target mediated hepatotoxicity issues. In the present study, we investigated hepatic transcription profiles of mice receiving non-toxic and toxic LNA gapmers after a single and repeat administration. To understand the mechanism of LNA gapmer-induced heptotoxicity in mice, we investigated the transcription profiles of liver RNA isolated from mice receiving non-toxic sequence (NTS-1), toxic sequence (TS-2), or severely toxic sequence (HTS-3) of LNA gapmers at 25 mg/kg (dose volume of 10 mL/kg) at 8, 16, or 72 hrs after a single administration (by subcutaneous injection ) using microarray analysis. We also investigated the transcription profiles of liver RNA isolated from mice receiving non-toxic sequence (NTS-1) or toxic sequence (TS-2) of LNA gapmers at 25 mg/kg (dose volume of 10 mL/kg) at 2 weeks after repeated administration (by subcutaneous injection ) using microarray analysis.
2014-01-08 | E-GEOD-53230 | biostudies-arrayexpress
Project description:Development of LNA gapmers, antisense oligonucleotides used for efficient inhibition of target RNA expression, is limited by non-target mediated hepatotoxicity issues. In the present study, we investigated hepatic transcription profiles of mice receiving non-toxic and toxic LNA gapmers after a single and repeat administration.
2014-01-08 | GSE53230 | GEO
Project description:Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver MicroRNA-122 (miR-122) is an abundant liver-specific miRNA, implicated in fatty acid and cholesterol metabolism as well as hepatitis C viral replication. Here, we report that a systemically administered 16-nt, unconjugated LNA (locked nucleic acid)-antimiR oligonucleotide complementary to the 5' end of miR-122 leads to specific, dose-dependent silencing of miR-122 and shows no hepatotoxicity in mice. Antagonism of miR-122 is due to formation of stable heteroduplexes between the LNA-antimiR and miR-122 as detected by northern analysis. Fluorescence in situ hybridization demonstrated uptake of the LNA-antimiR in mouse liver cells, which was accompanied by markedly reduced hybridization signals for mature miR-122 in treated mice. Functional antagonism of miR-122 was inferred from a low cholesterol phenotype and de-repression within 24 h of 199 liver mRNAs showing significant enrichment for miR-122 seed matches in their 3' UTRs. Expression profiling extended to 3 weeks after the last LNA-antimiR dose revealed that most of the changes in liver gene expression were normalized to saline control levels coinciding with normalized miR-122 and plasma cholesterol levels. Combined, these data suggest that miRNA antagonists comprised of LNA are valuable tools for identifying miRNA targets in vivo and for studying the biological role of miRNAs and miRNA-associated gene-regulatory networks in a physiological context. Keywords: compound treatment
2008-12-16 | GSE13948 | GEO
Project description:Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver; MicroRNA-122 (miR-122) is an abundant liver-specific miRNA, implicated in fatty acid and cholesterol metabolism as well as hepatitis C viral replication. Here, we report that a systemically administered 16-nt, unconjugated LNA (locked nucleic acid)-antimiR oligonucleotide complementary to the 5' end of miR-122 leads to specific, dose-dependent silencing of miR-122 and shows no hepatotoxicity in mice. Antagonism of miR-122 is due to formation of stable heteroduplexes between the LNA-antimiR and miR-122 as detected by northern analysis. Fluorescence in situ hybridization demonstrated uptake of the LNA-antimiR in mouse liver cells, which was accompanied by markedly reduced hybridization signals for mature miR-122 in treated mice. Functional antagonism of miR-122 was inferred from a low cholesterol phenotype and de-repression within 24 h of 199 liver mRNAs showing significant enrichment for miR-122 seed matches in their 3' UTRs. Expression profiling extended to 3 weeks after the last LNA-antimiR dose revealed that most of the changes in liver gene expression were normalized to saline control levels coinciding with normalized miR-122 and plasma cholesterol levels. Combined, these data suggest that miRNA antagonists comprised of LNA are valuable tools for identifying miRNA targets in vivo and for studying the biological role of miRNAs and miRNA-associated gene-regulatory networks in a physiological context. Experiment Overall Design: Female NMRI mice were treated at day 2 with either 25mg/kg antimiR-122 (SPC3372) or vehicle (saline). Mice were sacrificied at day 3, 9 and 23 and liver RNA assayed. Three biological replicates for each of the six groups.
2009-01-13 | E-GEOD-13948 | biostudies-arrayexpress
Project description:Rat has been treated with different compounds with the purpose of investigating toxicological mechanisms. But toxic and non-toxic compounds has been administered. 3 toxic (ANIT, DMN, NMF) 3 non-tox (Caerulein, dinitrophenol(DNP), Rosiglitazone) in 5-plicates (30 arrays in all) and 9 untreated (control), 39 samples in all. The array data was used to identify genes with biomarker potential for detecting toxic properties of compounds. Keywords: other Rats was treated with different compounds and RNA from liver was extracyed after 48 hours. Microarrays (GeneChip Rat230 version 2) was run on the RNA
2006-08-11 | E-GEOD-5509 | biostudies-arrayexpress
Project description:Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR
| PRJNA110285 | ENA
Project description:In this study, female DO mice were administered zileuton or vehicle i.g. daily for seven days, and assessed for the toxic outcomes in the livers. In addition to the clinical and histopathological assessment, RNA-seq analysis was performed to identify the differentially expressed genes in animals susceptible to the zileuton toxicity. Pathway analysis on the differentially expressed genes was performed to investigate the molecular mechanisms underlying the sensitivity to the liver toxicity.
2019-11-27 | GSE141089 | GEO
Project description:To characterize gene expression changes in arachidonic acid metabolism pathway genes in the presense of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) mice administered were administered an atherogenic diet for a period of four weeks. Administration of the atherogenic diet resulted in significant enrichment of the arachidonic acid metabolism pathway by gene set enrichment analysis (GSEA). The core enrichment subset of genes was down-regulated in mice administered the atherogenic diet and the majority of the genes that were down-regulated were cytochrome P450s.
2014-01-03 | GSE53381 | GEO
Project description:To characterize gene expression changes in arachidonic acid metabolism pathway genes in the presense of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) mice administered were administered an atherogenic diet for a period of four weeks. Administration of the atherogenic diet resulted in significant enrichment of the arachidonic acid metabolism pathway by gene set enrichment analysis (GSEA). The core enrichment subset of genes was down-regulated in mice administered the atherogenic diet and the majority of the genes that were down-regulated were cytochrome P450s. A total of 4 wild-type mice were administered a standard diet (STD; control group) and 4 wild-type mice were administered a HFHC diet (HFHC).
2014-01-03 | E-GEOD-53381 | biostudies-arrayexpress
Project description:Bacterial superantigens are virulence factors that cause toxic shock syndrome. Here, the genome-wide, temporal response of mice to lethal intranasal staphylococcal enterotoxin B (SEB) was investigated in six tissues (PBMC, lung, spleen, kidney, heart, Liver).The earliest responses and largest number of affected genes occurred in tissues (PBMCs, spleen and lung) with the highest content of both T-cells and monocyte/macrophages, the direct cellular targets of SEB. In contrast, the response of liver, kidney and heart was delayed and involved fewer genes, but revealed a dominant genetic program that was seen in all 6 tissues. Many of the 85 uniquely annotated transcripts participating in this shared genomic response have not been previously linked to SEB. Global gene-expression changes measured serially across multiple organs identified new candidate mechanisms of SEB-induced death. Toxin or saline (control) was administered to male C3H/HeJ mice in 5 independent experiments. Toxin or saline was administered i.n. followed by an i.p dose two hours later. Lung, liver, heart, spleen and kidney were harvest and preserved for tRNA purification at each time point. Each PBMC sample corresponded to a pooled sample (10 mice per time point). Samples from control animals were collected at time 0, 2.75 h, 5 h and 24 h. Samples from SEB treatment were collected at 0h, 2.75h, 5 h and 24 h. Only 4 set of samples per tissue type were used for microarray.
2014-03-01 | E-GEOD-52474 | biostudies-arrayexpress