Mus musculus
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PROVIDER: PRJNA93161 | ENA |
REPOSITORIES: ENA
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Project description:In this study we used the d337T TRb transgenic mouse that has been created to reproduce the human genetic disease known as resistance to thyroid hormone (RTH) as a model to determine if the d337T TRb mutation would have an effect on PPARa activation. A single amino acid deletion (d337T) abrogates thyroid hormone (T3) binding and transforms the thyroid hormone receptor (TRb) into a constitutive repressor. The principle goal was to determine if T3 regulates myocardial energy metabolism through its nuclear receptors. We introduced a known PPARa activator (WY14, 643) into control and d337T TRb transgenic mice then examined cardiac gene expression using Affymetrix 430_2 expression arrays and RT-PCR. We compared the gene expression of PPARa, RXRb and TRa,b and three PPARa target genes among four studies groups [control, control with WY14, 643, d337T TRb, and d337T TRb with WY14, 643] consisting of seven mice per group. Microarray analysis revealed that these genes responded to the WY14, 643 treatments of control and d337T TRb mice. Analysis of the array and RT-PCR data indicates that mRNA expression levels of PPARa and mRXRb decrease after a six hour drug treatment in both control and d337T TRb mice (P<0.01) as did the array mRNA expression levels for TRa & b (P<0.025). Three target genes (AMPD3, PDK4 and UCP3) of PPARa were up regulated in control and down regulated in the d337T TRb transgenic mouse, indicating a direct action on these metabolic genes when the TRb becomes a repressor. In conclusion, PPARa activation by WY14, 643 has a positive effect on control mice and a negative effect on the TRb transgenic mice which supports our hypothesis that T3 regulates myocardial energy metabolism through its nuclear receptors. Experiment Overall Design: 7 control, 7 deletion strain individuals, 7 controls with a PPARalpha activator, 7 deletion strain individuals with a PPARalpha activator
2007-11-22 | E-GEOD-3067 | biostudies-arrayexpress
Project description:In this study we used the d337T TRb transgenic mouse that has been created to reproduce the human genetic disease known as resistance to thyroid hormone (RTH) as a model to determine if the d337T TRb mutation would have an effect on PPARa activation. A single amino acid deletion (d337T) abrogates thyroid hormone (T3) binding and transforms the thyroid hormone receptor (TRb) into a constitutive repressor. The principle goal was to determine if T3 regulates myocardial energy metabolism through its nuclear receptors. We introduced a known PPARa activator (WY14, 643) into control and d337T TRb transgenic mice then examined cardiac gene expression using Affymetrix 430_2 expression arrays and RT-PCR. We compared the gene expression of PPARa, RXRb and TRa,b and three PPARa target genes among four studies groups [control, control with WY14, 643, d337T TRb, and d337T TRb with WY14, 643] consisting of seven mice per group. Microarray analysis revealed that these genes responded to the WY14, 643 treatments of control and d337T TRb mice. Analysis of the array and RT-PCR data indicates that mRNA expression levels of PPARa and mRXRb decrease after a six hour drug treatment in both control and d337T TRb mice (P<0.01) as did the array mRNA expression levels for TRa & b (P<0.025). Three target genes (AMPD3, PDK4 and UCP3) of PPARa were up regulated in control and down regulated in the d337T TRb transgenic mouse, indicating a direct action on these metabolic genes when the TRb becomes a repressor. In conclusion, PPARa activation by WY14, 643 has a positive effect on control mice and a negative effect on the TRb transgenic mice which supports our hypothesis that T3 regulates myocardial energy metabolism through its nuclear receptors. Keywords: treatment and deletion effects
2005-09-26 | GSE3067 | 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:Investigation of thyroid hormone induced gene expression in liver tissue of different thyroid hormone receptor mutants
| PRJNA362619 | ENA
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: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: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
Project description:Transcriptional activation by the thyroid hormone receptor through ligand dependent receptor recruitment and chromatin remodeling
| PRJNA275427 | ENA