Mus musculus
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ABSTRACT:
PROVIDER: PRJNA232848 | ENA |
REPOSITORIES: ENA
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Project description:Two long and one truncated isoforms (termed LAP*, LAP, and LIP, respectively) of the transcription factor CCAAT enhancer binding protein beta (C/EBPβ) are expressed from a single intronless Cebpb gene by alternative translation initiation. Isoform expression is sensitive to mammalian target of rapamycin (mTOR)-mediated activation of the translation initiation machinery and relayed through an upstream open reading frame (uORF) on the C/EBPβ mRNA. The truncated C/EBPβ LIP, initiated by high mTOR activity, has been implied in neoplasia, but it was never shown whether endogenous C/EBPβ LIP may function as an oncogene. In this study, we examined spontaneous tumor formation in C/EBPβ knockin mice that constitutively express only the C/EBPβ LIP isoform from its own locus. Our data show that deregulated C/EBPβ LIP predisposes to oncogenesis in many tissues. Gene expression profiling suggests that C/EBPβ LIP supports a protumorigenic microenvironment, resistance to apoptosis, and alteration of cytokine/chemokine expression. The results imply that enhanced translation reinitiation of C/ EBPβ LIP promotes tumorigenesis. Accordingly, pharmacological restriction of mTOR function might be a therapeutic option in tumorigenesis that involves enhanced expression of the truncated C/EBPβ LIP isoform.
2014-12-16 | GSE53770 | GEO
Project description:Two long and one truncated isoforms (termed LAP*, LAP, and LIP, respectively) of the transcription factor CCAAT enhancer binding protein beta (C/EBPM-NM-2) are expressed from a single intronless Cebpb gene by alternative translation initiation. Isoform expression is sensitive to mammalian target of rapamycin (mTOR)-mediated activation of the translation initiation machinery and relayed through an upstream open reading frame (uORF) on the C/EBPM-NM-2 mRNA. The truncated C/EBPM-NM-2 LIP, initiated by high mTOR activity, has been implied in neoplasia, but it was never shown whether endogenous C/EBPM-NM-2 LIP may function as an oncogene. In this study, we examined spontaneous tumor formation in C/EBPM-NM-2 knockin mice that constitutively express only the C/EBPM-NM-2 LIP isoform from its own locus. Our data show that deregulated C/EBPM-NM-2 LIP predisposes to oncogenesis in many tissues. Gene expression profiling suggests that C/EBPM-NM-2 LIP supports a protumorigenic microenvironment, resistance to apoptosis, and alteration of cytokine/chemokine expression. The results imply that enhanced translation reinitiation of C/ EBPM-NM-2 LIP promotes tumorigenesis. Accordingly, pharmacological restriction of mTOR function might be a therapeutic option in tumorigenesis that involves enhanced expression of the truncated C/EBPM-NM-2 LIP isoform. A cohort of C/EBPb LIP heterozygous (+/L) and wild type (+/+) mice were kept over 25 months and animals showing palpable lymphoma were sacrificed. The lymphoma developed spontaneously. For each genotype, 5 lymphoma were used for RNA preparation and gene expression profiling analysis.
2014-12-16 | E-GEOD-53770 | biostudies-arrayexpress
Project description:C/EBPβ plays a major role in numerous biological processes but unfortunately its precise role is not still clear and conflicting studies showed that this transcription factor could have contradictory functions. These latter arise from the complexity of mechanisms regulating C/EBPβ activity. Indeed, C/EBPβ encodes an intronless gene that generates a single mRNA that is alternatively translated into two major isoforms of 35kDa (liver-enriched activator protein: LAP) and 20kDa (liver-enriched inhibitory protein: LIP). LAP is the active isoform of this transcription factor whereas LIP, a truncated isoform negatively regulate C/EBPβ-LAP-mediated gene expression. The main goal of our research was to understand how LAP and LIP isoforms governe C/EBPβ cellular functions with the identification of new genes and pathways regulated by these isoforms in the human Hep3B hepatoma cell line. For this purpose an original in vitro system characterized by a target genes induction with the activatory C/EBPß isoform LAP and a target genes repression with the inhibitory C/EBPß isoform (LIP) was used to identify the genuine C/EBPβ molecular signature. Using a cDNA microarray which provides a complete coverage of the liver transcriptome, we identified 676 genes inversely regulated by LAP and LIP. These selected genes are involved in many biological processes as the hepatic metabolism (cholesterol), detoxification, induction of apoptosis and negative regulation of the cell proliferation. According to the involvement of C/EBPβ in hepatic carcinogenesis we focused on cell cycle regulation and apoptosis. Through functional studies, we proved for the first time that LIP plays in favor of the survival of the Hep3B cells whereas LAP makes the cells more sensitive to staurosporine-induced cell death. Moreover, a lot of studies demonstrated that the anti-proliferative action of C/EBPβ mainly depends on RB protein. By studying the rate of Hep3B cells proliferation which overexpress LAP, we brought to the fore that this isoform would be able to induce a repression of the Hep3B cells line proliferation - a RB- and p53- negative cell line. Thus, LAP seems able to induce the repression of proliferation by a different metabolic way from the RB one. Keywords: comparison of cells expressing LAP or LIP RNA were extracted from 5 Hep3BLAPexpressing LAP, 5 Hep3BLAP control without expression of LAP, 5 Hep3BLIP expressing LIP and 5 Hep3BLIP control without epression of LIP. Each sample was hybridized once in 5 different nylon membranes.
2011-01-16 | E-GEOD-12410 | biostudies-arrayexpress
Project description:C/EBPβ plays a major role in numerous biological processes but unfortunately its precise role is not still clear and conflicting studies showed that this transcription factor could have contradictory functions. These latter arise from the complexity of mechanisms regulating C/EBPβ activity. Indeed, C/EBPβ encodes an intronless gene that generates a single mRNA that is alternatively translated into two major isoforms of 35kDa (liver-enriched activator protein: LAP) and 20kDa (liver-enriched inhibitory protein: LIP). LAP is the active isoform of this transcription factor whereas LIP, a truncated isoform negatively regulate C/EBPβ-LAP-mediated gene expression. The main goal of our research was to understand how LAP and LIP isoforms governe C/EBPβ cellular functions with the identification of new genes and pathways regulated by these isoforms in the human Hep3B hepatoma cell line. For this purpose an original in vitro system characterized by a target genes induction with the activatory C/EBPß isoform LAP and a target genes repression with the inhibitory C/EBPß isoform (LIP) was used to identify the genuine C/EBPβ molecular signature. Using a cDNA microarray which provides a complete coverage of the liver transcriptome, we identified 676 genes inversely regulated by LAP and LIP. These selected genes are involved in many biological processes as the hepatic metabolism (cholesterol), detoxification, induction of apoptosis and negative regulation of the cell proliferation. According to the involvement of C/EBPβ in hepatic carcinogenesis we focused on cell cycle regulation and apoptosis. Through functional studies, we proved for the first time that LIP plays in favor of the survival of the Hep3B cells whereas LAP makes the cells more sensitive to staurosporine-induced cell death. Moreover, a lot of studies demonstrated that the anti-proliferative action of C/EBPβ mainly depends on RB protein. By studying the rate of Hep3B cells proliferation which overexpress LAP, we brought to the fore that this isoform would be able to induce a repression of the Hep3B cells line proliferation - a RB- and p53- negative cell line. Thus, LAP seems able to induce the repression of proliferation by a different metabolic way from the RB one. Keywords: comparison of cells expressing LAP or LIP
2011-01-16 | GSE12410 | GEO
Project description:Synthesis of the metabolic transcription factor C/EBPβ-LIP is stimulated by mTORC1, which critically depends on a short upstream open reading frame (uORF) in the C/EBPβ-mRNA. We tested if that reduced C/EBPβ-LIP expression due to genetic ablation of the uORF delays the development of age-associated phenotypes in mice.
2019-01-16 | E-MTAB-6435 | biostudies-arrayexpress
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:Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P. leucopus in aging studies. Notably, P. leucopus exhibits distinct body composition characteristics, emphasizing reduced muscle force exertion and a unique metabolism, particularly in fat mass. Cardiovascular assessments showed changes in arterial stiffness, challenging conventional assumptions and highlighting the need for a nuanced interpretation of aging-related phenotypes. Our study also highlights inherent challenges associated with maintaining and phenotyping P. leucopus cohorts. Behavioral considerations, including anxiety-induced responses during handling and phenotyping assessment, pose obstacles in acquiring meaningful data. Moreover, the unique anatomy of P. leucopus necessitates careful adaptation of protocols designed for Mus musculus. While showcasing potential benefits, further extensive analyses across broader age ranges and larger cohorts are necessary to establish the reliability of P. leucopus as a robust and translatable model for aging studies.
| S-EPMC11335981 | biostudies-literature
Project description:BackgroundCopy number variation is an important dimension of genetic diversity and has implications in development and disease. As an important model organism, the mouse is a prime candidate for copy number variant (CNV) characterization, but this has yet to be completed for a large sample size. Here we report CNV analysis of publicly available, high-density microarray data files for 351 mouse tail samples, including 290 mice that had not been characterized for CNVs previously.ResultsWe found 9634 putative autosomal CNVs across the samples affecting 6.87% of the mouse reference genome. We find significant differences in the degree of CNV uniqueness (single sample occurrence) and the nature of CNV-gene overlap between wild-caught mice and classical laboratory strains. CNV-gene overlap was associated with lipid metabolism, pheromone response and olfaction compared to immunity, carbohydrate metabolism and amino-acid metabolism for wild-caught mice and classical laboratory strains, respectively. Using two subspecies of wild-caught Mus musculus, we identified putative CNVs unique to those subspecies and show this diversity is better captured by wild-derived laboratory strains than by the classical laboratory strains. A total of 9 genic copy number variable regions (CNVRs) were selected for experimental confirmation by droplet digital PCR (ddPCR).ConclusionThe analysis we present is a comprehensive, genome-wide analysis of CNVs in Mus musculus, which increases the number of known variants in the species and will accelerate the identification of novel variants in future studies.
| S-EPMC4490682 | biostudies-literature
Project description:BackgroundLong terminal repeat (LTR) retrotransposons make up a large fraction of the typical mammalian genome. They comprise about 8% of the human genome and approximately 10% of the mouse genome. On account of their abundance, LTR retrotransposons are believed to hold major significance for genome structure and function. Recent advances in genome sequencing of a variety of model organisms has provided an unprecedented opportunity to evaluate better the diversity of LTR retrotransposons resident in eukaryotic genomes.ResultsUsing a new data-mining program, LTR_STRUC, in conjunction with conventional techniques, we have mined the GenBank mouse (Mus musculus) database and the more complete Ensembl mouse dataset for LTR retrotransposons. We report here that the M. musculus genome contains at least 21 separate families of LTR retrotransposons; 13 of these families are described here for the first time.ConclusionsAll families of mouse LTR retrotransposons are members of the gypsy-like superfamily of retroviral-like elements. Several different families of unrelated non-autonomous elements were identified, suggesting that the evolution of non-autonomy may be a common event. High sequence similarity between several LTR retrotransposons identified in this study and those found in distantly-related species suggests that horizontal transfer has been a significant factor in the evolution of mouse LTR retrotransposons.
| S-EPMC395764 | biostudies-literature
Project description:House mice (Mus musculus) emit ultrasonic vocalizations (USVs), which are surprisingly complex and have features of bird song, but their functions are not well understood. Previous studies have reported mixed evidence on whether there are sex differences in USV emission, though vocalization rate or other features may depend upon whether potential receivers are of the same or opposite sex. We recorded the USVs of wild-derived adult house mice (F1 of wild-caught Mus musculus musculus), and we compared the vocalizations of males and females in response to a stimulus mouse of the same- or opposite-sex. To detect and quantify vocalizations, we used an algorithm that automatically detects USVs (Automatic Mouse Ultrasound Detector or A-MUD). We found high individual variation in USV emission rates (4 to 2083 elements/10 min trial) and a skewed distribution, with most mice (60%) emitting few (≤50) elements. We found no differences in the rates of calling between the sexes overall, but mice of both sexes emitted vocalizations at a higher rate and higher frequencies during opposite- compared to same-sex interactions. We also observed a trend toward higher amplitudes by males when presented with a male compared to a female stimulus. Our results suggest that mice modulate the rate and frequency of vocalizations depending upon the sex of potential receivers.
| S-EPMC5728457 | biostudies-literature