Mus musculus
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PROVIDER: PRJNA267112 | ENA |
REPOSITORIES: ENA
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Project description:Identifying the early gene program induced by GnRH would help understand how GnRH-activated signaling pathways modulate gonadotrope secretory response. We previously analyzed GnRH-induced early genes in LbT2 cells, however these lack GnRH self-potentiation, a physiological attribute of gonadotropes. To minimize cellular heterogeneity, rat primary pituitary cultures were enriched for gonadotropes by 40-60% using a sedimentation gradient. Given the limited number of gonadotropes, RNA was amplified prior to microarray analysis. Thirty-three genes were up-regulated 40 minutes after GnRH stimulation. Real-time PCR confirmed regulation of several transcripts including fosB, c-fos, egr-2 and rap1b, a small GTPase and member of the Ras family. GnRH stimulated rap1b gene expression in gonadotropes, measured by a sensitive single cell assay. Immunocytochemistry revealed increased Rap1 protein in GnRH-stimulated gonadotropes. These data establish rap1b as a novel gene rapidly induced by GnRH and a candidate to modulate gonadotropin secretion in rat gonadotropes. Primary rat gonadotrope cells were exposed to 10 nM GnRH for 40 min, then harvested and processed for RNA extraction using a Qiagen RNeasy mini kit (Qiagen, Valencia, CA). A total of 12 Affymetrix Rat Expression Array 230 v2.0, namely 6 GnRH-treated and 6 vehicle-treated samples, each containing 31,000 gene clusters, were used. Data analysis was performed by Affymetrix GeneChip Operating System (GCOS). A gene was considered to be up-regulated by GnRH if there is at least 50% concordance across multiple pairwise comparisons of GnRH- vs. vehicle-treated microarrays, and if the fold-change was at least 1.50.
2011-08-16 | E-GEOD-31399 | biostudies-arrayexpress
Project description:Mouse immortalized LbetaT2 gonadotrope cells treated with 100 nM GnRH for 2 h. GnRH treated LbetaT2 cells vs. untreated to assess whether GnRH regulates miRNA expression acutely. Treated and untreated RNA labeled independently then hybridized together to 2-color array. Duplicate arrays run with RNA from independent experiments.
2011-02-18 | E-GEOD-27398 | biostudies-arrayexpress
Project description:Mouse immortalized LbetaT2 gonadotrope cells treated with 100 nM GnRH for 2 h.
2011-02-18 | GSE27398 | GEO
Project description:Gonadotropin-releasing hormone (GnRH) is secreted in brief pulses from the hypothalamus. GnRH regulates follicle-stimulating hormone b-subunit (FSHb) gene expression in pituitary gonadotropes in a frequency-sensitive manner that is central to reproductive physiology. The mechanisms underlying the preferential and paradoxical induction of FSHb by low frequency GnRH pulses are incompletely understood. Here, we identify growth differentiation factor 9 (GDF9) as a novel autocrine inducer of FSHb gene expression. GDF9 gene expression was preferentially suppressed by high frequency GnRH pulses due to reduced transcription. Exogenous GDF9 induced FSHb mRNA expression and knockdown or immunoneutralization of GDF9 reduced FSHb gene expression. Treatment with GDF9 stimulated Smad2/3 phosphorylation. The activin receptor-like kinase (ALK) receptor inhibitor SB-505124 antagonized GDF9-induced Smad2/3 phosphorylation and FSHb mRNA induction. Smad2 and Smad3 knockdown studies indicated that the induction of FSHb by GDF9 involves both Smad2 and Smad3. GDF9 and GnRH synergistically induced FSHb mRNA expression and high frequency GnRH pulses suppressed GDF9. We hypothesized that GDF9 contributes to a regulatory loop that tunes the GnRH frequency-response characteristics of the FSHb gene. To test this, we determined the effects of GDF9 knockdown on FSHb induction at different GnRH pulse frequencies using a parallel perifusion system. Reduction of GDF9 shifted the characteristic pattern of GnRH pulse frequency sensitivity. These results identify GDF9 as contributing to an incoherent feed-forward loop, comprised of both intracellular and secreted elementscomponents, that regulates FSHb expression in response to activation of the cell surface GnRH receptor. LbT2 microarray datasets as well as RNA-Seq data (GSE42120) were interrogated to determine the levels of expression of ALK4/5/7.
2013-11-22 | GSE52631 | GEO
Project description:Sex differences in liver gene expression are dictated by sex-differences in circulating growth hormone (GH) profiles. Presently, the pituitary hormone dependence of mouse liver gene expression was investigated on a global scale to discover sex-specific early GH response genes that might contribute to sex-specific regulation of downstream GH targets and to ascertain whether intrinsic sex-differences characterize hepatic responses to plasma GH stimulation. RNA expression analysis using 41,000-feature microarrays revealed two distinct classes of sex-specific mouse liver genes: genes subject to positive regulation (class-I) and genes subject to negative regulation by pituitary hormones (class-II). Genes activated or repressed in hypophysectomized (Hypox) mouse liver within 30-90min of GH pulse treatment at a physiological dose were identified as direct targets of GH action (early response genes). Intrinsic sex-differences in the GH responsiveness of a subset of these early response genes were observed. Notably, 45 male-specific genes, including five encoding transcriptional regulators that may mediate downstream sex-specific transcriptional responses, were rapidly induced by GH (within 30min) in Hypox male but not Hypox female mouse liver. The early GH response genes were enriched in 29 male-specific targets of the transcription factor Mef2, whose activation in hepatic stellate cells is associated with liver fibrosis leading to hepatocellular carcinoma, a male-predominant disease. Thus, the rapid activation by GH pulses of certain sex-specific genes is modulated by intrinsic sex-specific factors, which may be associated with prior hormone exposure (epigenetic mechanisms) or genetic factors that are pituitary-independent, and could contribute to sex-differences in predisposition to liver cancer or other hepatic pathophysiologies.
2010-01-27 | GSE17644 | GEO
Project description:Gonadotropin-releasing hormone (GnRH) is secreted in brief pulses from the hypothalamus. GnRH regulates follicle-stimulating hormone b-subunit (FSHb) gene expression in pituitary gonadotropes in a frequency-sensitive manner that is central to reproductive physiology. The mechanisms underlying the preferential and paradoxical induction of FSHb by low frequency GnRH pulses are incompletely understood. Here, we identify growth differentiation factor 9 (GDF9) as a novel autocrine inducer of FSHb gene expression. GDF9 gene expression was preferentially suppressed by high frequency GnRH pulses due to reduced transcription. Exogenous GDF9 induced FSHb mRNA expression and knockdown or immunoneutralization of GDF9 reduced FSHb gene expression. Treatment with GDF9 stimulated Smad2/3 phosphorylation. The activin receptor-like kinase (ALK) receptor inhibitor SB-505124 antagonized GDF9-induced Smad2/3 phosphorylation and FSHb mRNA induction. Smad2 and Smad3 knockdown studies indicated that the induction of FSHb by GDF9 involves both Smad2 and Smad3. GDF9 and GnRH synergistically induced FSHb mRNA expression and high frequency GnRH pulses suppressed GDF9. We hypothesized that GDF9 contributes to a regulatory loop that tunes the GnRH frequency-response characteristics of the FSHb gene. To test this, we determined the effects of GDF9 knockdown on FSHb induction at different GnRH pulse frequencies using a parallel perifusion system. Reduction of GDF9 shifted the characteristic pattern of GnRH pulse frequency sensitivity. These results identify GDF9 as contributing to an incoherent feed-forward loop, comprised of both intracellular and secreted elementscomponents, that regulates FSHb expression in response to activation of the cell surface GnRH receptor. LbT2 microarray datasets as well as RNA-Seq data (GSE42120) were interrogated to determine the levels of expression of ALK4/5/7. LM-NM-2T2 cells were transfected with either scrambled siRNA or Gas siRNA for 48 h. RNA samples were snap-frozen in dry ice prior to whole-genome expression profiling analysis using MouseWG-6 v2.0 Expression BeadChip (Illumina, San Diego, CA). A total of 6 concentrated conditioned media samples were independently prepared: 3 replicates from control siRNA-treated cells, and 3 replicates from Gas siRNA-treated cells. This submission represents the microarray component of study.
2013-11-22 | E-GEOD-52631 | 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:Identifying the early gene program induced by GnRH would help understand how GnRH-activated signaling pathways modulate gonadotrope secretory response. We previously analyzed GnRH-induced early genes in LbT2 cells, however these lack GnRH self-potentiation, a physiological attribute of gonadotropes. To minimize cellular heterogeneity, rat primary pituitary cultures were enriched for gonadotropes by 40-60% using a sedimentation gradient. Given the limited number of gonadotropes, RNA was amplified prior to microarray analysis. Thirty-three genes were up-regulated 40 minutes after GnRH stimulation. Real-time PCR confirmed regulation of several transcripts including fosB, c-fos, egr-2 and rap1b, a small GTPase and member of the Ras family. GnRH stimulated rap1b gene expression in gonadotropes, measured by a sensitive single cell assay. Immunocytochemistry revealed increased Rap1 protein in GnRH-stimulated gonadotropes. These data establish rap1b as a novel gene rapidly induced by GnRH and a candidate to modulate gonadotropin secretion in rat gonadotropes.
2011-08-17 | GSE31399 | GEO
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