Mus musculus
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ABSTRACT:
PROVIDER: PRJNA232530 | ENA |
REPOSITORIES: ENA
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Project description:Due to its high throughput nature, toxicogenomics can provide a broad picture of a toxic response, offering the ideal functional platform for grouping chemicals according to mechanistic similarity. In this way, toxicogenomics has found its way into predictive toxicology. However, so far, the predictive potential of toxicogenomics in an endocrine disruptive screening context has not been extensively examined. The aim of this study was to combine a toxicogenomics approach with an estrogen-sensitive MCF-7 cell system. In total, 18 compounds with endocrine disruptive potential were selected, of which 11 are listed as ICCVAM reference compounds for validation of estrogen receptor (ER) binding and transactivation assays. In this way, the grouping and classification potential of the gene expression profiles could be directly compared to the more classical estrogenicity screens, such as ER binding, ER transactivation and MCF-7 cell proliferation assays. Results indicated that this toxicogenomics approach was clearly capable of grouping compounds into strong, weak and non estrogenic groups. This demonstrates the value of toxicogenomics for evaluating gradual differences in related modes of action, in addition to the more common search for opposite modes of action. The chemical groups were represented by interesting marker genes such as PGR, ERBB2, CXCL12, AREG and EGR3, including some early-responsive (4h) potential biomarkers. These results open the discussion on the added value of a broader endpoint evaluation in estrogenicity screens provided by omics-techniques compared to the classical single endpoint based assays.
2015-10-01 | GSE16881 | GEO
Project description:Under REACH, the European Community Regulation on chemicals, the testing strategy for carcinogenicity is generally based on in vitro and in vivo genotoxicity assays. Given that non-genotoxic carcinogens are negative for genotoxicity, this class of carcinogens will not be detected. Therefore, alternative test are urgently needed. Non-genotoxic carcinogens, however, act through different modes of action, which complicates the development of such an assay. The aim of this study was to investigate whether gene expression profiling in primary mouse hepatocytes can be used to distinguish different modes of action of non-genotoxic carcinogens. Primary mouse hepatocytes were exposed to 16 non-genotoxic carcinogens with diverse modes of action. Upon profiling, pathway analysis was performed to obtain insight into the biological relevance of the observed changes in gene expression. To recognize similarities in mode of action at the transcriptomic level, both a supervised and an unsupervised comparison approach was applied.
2012-06-25 | E-GEOD-35058 | biostudies-arrayexpress
Project description:The current test strategy for carcinogenicity is generally based on in vitro and in vivo genotoxicity assays. Non-genotoxic carcinogens (NGTXC) are negative for genotoxicity and go undetected. Therefore, alternative tests to detect these chemicals are urgently needed. NGTXC act through different modes of action, which complicates the development of such assays. We have demonstrated recently in primary mouse hepatocytes that some, but certainly not all, NGTXC can be categorized according to their mode of action based on feature detection at a gene expression level (Schaap et al. 2012 (PMID 22710402)). Identification of a wider range of chemicals probably requires multiple in vitro systems. In the current study, we describe the added value of using mouse embryonic stem cells. In this study, the focus is on NGTXC, but we also included genotoxic carcinogens and non-carcinogens. This approach enables us to assess the robustness of this method and to evaluate the system for recognizing features of chemicals in general, which is important for application in future risk assessment. Primary mouse hepatocytes and mouse embryonic stem cells were exposed to 26 chemicals (non-genotoxic carcinogens and non-carcinogens) representing diverse modes of action. Upon profiling, an unsupervised comparison approach was applied to recognize similar features at the transcriptomic level. This Series consists of the gene expression data of the primary mouse hepatocytes. The expression data of the mouse embryonic stem cells is submitted separately under another accession number. In this study we tested 26 chemicals of which 16 non-genotoxic carcinogens, 4 genotoxic carcinogens, 2 genotoxic non-carcinogens and 4 non-carcinogens. Specification of the chemicals can be found in the readme file.
2014-10-23 | E-GEOD-44088 | biostudies-arrayexpress
Project description:The current test strategy for carcinogenicity consists initially of in vivo and in vitro genotoxicity tests. Non-genotoxic carcinogens do not directly induce DNA damage and, as such, go undetected under this test strategy. In a previous study we setup a comparison approach to categorize chemicals having similar modes of action, according to similarity in gene expression. In the current study we will investigate whether this comparison approach can be improved by omptimizing the concentration selection procedure and by testing a concentration range per chemical.
2016-12-23 | GSE53634 | GEO
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
| S-EPMC8784167 | biostudies-literature
Project description:To describe the protein profile in hippocampus, colon and ileum tissue’ changing after the old faeces transplants, we adopted a quantitative label free proteomics approach.
2021-09-09 | PXD016432 | Pride
Project description:We tested the hypothesis that BHT is an endocrine disruptor by using a Next Generation Risk Assessment (NGRA) method. Four different cell lines: A549, HCC1428, HepG2 and MCF7 were treated with BHT and a series of BHT analogs at 5 different concentrations, RNA was isolated from cell extracts and run on the L1000 gene array platform. A toxicogenomics-based assessment was performed by comparing BHT’s unique genomic signature to a large external database containing signatures of other compounds (including many known endocrine disruptors) to identify if any endocrine disruption-related modes of action (MoAs) are prevalent among BHT and other compounds with similar genomic signatures. In addition, we performed a toxicogenomics-based structure activity relationship (SAR) assessment of BHT and a series of structurally similar analogues to understand if endocrine disruption is a relevant MoA for chemicals that are considered suitable analogs to BHT using the P&G read across framework (Wu et al., 2010). The platform is GPL20573: Broad Institute Human L1000 epsilon http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL20573
2022-10-17 | GSE211553 | GEO
Project description:To characterize the genetic basis of hybrid male sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven ‘hotspots,’ seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL - but not cis eQTL - were substantially lower when mapping was restricted to a ‘fertile’ subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility.
2014-05-01 | GSE54089 | GEO
Project description:The aim of the study was to investigate whether the trefoil peptide genes, in concerted action with a miRNA regulatory network, were contributing to nutritional maintrenance. Using a Tff3 knock-out mouse model, 21 specific miRNAs were noted to be significantly deregulated when compared to the wild type strain.
2010-09-20 | GSE23819 | GEO
Project description:The aim of the study was to investigate whether the trefoil peptide genes, in concerted action with a miRNA regulatory network, were contributing to nutritional maintrenance. Using a Tff2 knock-out mouse model, 48 specific miRNAs were noted to be significantly deregulated when compared to the wild type strain.
2012-01-01 | GSE25815 | GEO