Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA112097 | ENA |
REPOSITORIES: ENA
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Project description:In skeletal muscle, STAT5a/b transcription factors are critical for normal postnatal growth, whole-animal glucose homeostasis, and local IGF-1 production. These observations have led us to hypothesize that STAT5a/b are critical for maintenance of normal muscle mass and function. To investigate this, mice with a skeletal muscle-specific deletion of the Stat5a/b genes (Stat5MKO) were used. Stat5MKO mice displayed reduced muscle mass, altered fiber-type distribution and reduced activity. On a molecular level, gene expression in skeletal muscle of Stat5MKO and control mice was analyzed by microarrays and real-time PCR, both in the presence and absence of growth hormone (GH) stimulation. Several genes involved in muscle growth, fiber-type and metabolism were significantly changed. Specifically in the quadriceps, a muscle almost exclusively composed of type II fibers, the absence of STAT5a/b led to increased expression of several genes associated with type I fibers and the de novo appearance of type I fibers. Additionally, it is shown here that expression of the androgen receptor gene (Ar) is controlled by GH through STAT5a/b. The link between STAT5a/b and Ar gene is likely through direct transcriptional regulation, as chromatin immunoprecipitaion of the Ar promoter region in C2C12 myoblasts was accomplished by antibodies against STAT5a. These experiments demonstrate an important role for STAT5a/b in skeletal muscle physiology and they provide a direct link to androgen signaling. Experiment Overall Design: Total 6 WT controls and 6 stat5a/b KO mice, treated or w/o GH
2009-09-05 | E-GEOD-14710 | biostudies-arrayexpress
Project description:In skeletal muscle, STAT5a/b transcription factors are critical for normal postnatal growth, whole-animal glucose homeostasis, and local IGF-1 production. These observations have led us to hypothesize that STAT5a/b are critical for maintenance of normal muscle mass and function. To investigate this, mice with a skeletal muscle-specific deletion of the Stat5a/b genes (Stat5MKO) were used. Stat5MKO mice displayed reduced muscle mass, altered fiber-type distribution and reduced activity. On a molecular level, gene expression in skeletal muscle of Stat5MKO and control mice was analyzed by microarrays and real-time PCR, both in the presence and absence of growth hormone (GH) stimulation. Several genes involved in muscle growth, fiber-type and metabolism were significantly changed. Specifically in the quadriceps, a muscle almost exclusively composed of type II fibers, the absence of STAT5a/b led to increased expression of several genes associated with type I fibers and the de novo appearance of type I fibers. Additionally, it is shown here that expression of the androgen receptor gene (Ar) is controlled by GH through STAT5a/b. The link between STAT5a/b and Ar gene is likely through direct transcriptional regulation, as chromatin immunoprecipitaion of the Ar promoter region in C2C12 myoblasts was accomplished by antibodies against STAT5a. These experiments demonstrate an important role for STAT5a/b in skeletal muscle physiology and they provide a direct link to androgen signaling. Keywords: stat5 KO or WT treated or w/o GH
2009-08-18 | GSE14710 | GEO
Project description:Skeletal muscle fiber composition and muscle energetics are not static and change in muscle disease. This study was performed to determine if a mitochondrial myopathy is associated with adjustments in skelatal fiber type composition. These effects of drug induced mitochondrial dysfunction on skeletal muscle fiber type composition were analyzed in an animal model.
2012-10-18 | E-MEXP-3642 | biostudies-arrayexpress
Project description:Skeletal muscle is a heterogeneous tissue consisting of blood vessels, connective tissue, and muscle fibers. The last are highly adaptive and can change their molecular composition depending on external and internal factors, such as exercise, age, and disease. Thus, examination of the skeletal muscles at the fiber type level is essential to detect potential alterations. Therefore, we established a protocol in which myosin heavy chain isoform immunolabeled muscle fibers were laser microdissected and separately investigated by mass spectrometry to develop advanced proteomic profiles of all murine skeletal muscle fiber types. Our in-depth mass spectrometric analysis revealed unique fiber type protein profiles, confirming fiber type-specific metabolic properties and revealing a more versatile function of type IIx fibers. Furthermore, we found that multiple myopathy-associated proteins were enriched in type I and IIa fibers. To further optimize the assignment of fiber types based on the protein profile, we developed a hypothesis-free machine-learning approach (available at: https://github.com/mpc-bioinformatics/FiPSPi), identified a discriminative peptide panel, and confirmed our panel using a public data set.
2021-06-07 | PXD025359 | Pride
Project description:This experiment was conducted to identify target genes of the microRNA-499 in skeletal muscle of transgenic mice that overexpressed miR-499. The following abstract from the submitted manuscript describes the major findings of this work. Coupling of mitochondrial function and skeletal muscle fiber type by a miR-499/Fnip1/AMPK circuit. Jing Liu, Xijun Liang, Danxia Zhou, Ling Lai, Tingting Fu, Yan Kong, Qian Zhou, Rick B. Vega, Min-Sheng Zhu, Daniel P. Kelly, Xiang Gao, and Zhenji Gan. Upon adaption of skeletal muscle to physiological and pathophysiological stimuli, muscle fiber type and mitochondrial function are coordinately regulated. Recent studies have identified pathways involved in control of contractile proteins of oxidative type fibers. However, the mechanism for coupling of mitochondrial function to muscle contractile machinery during fiber type transition remains unknown. Here, we show that the expression of the genes encoding type I myosins, Myh7/Myh7b and their intronic miR-208b/miR-499 parallels mitochondrial function during fiber type transitions. Using in vivo approaches in mice, we found that miR-499 drives a PGC-1a-dependent mitochondrial oxidative metabolism program to match shifts in slow-twitch muscle fiber composition. Mechanistically, miR-499 directly targets Fnip1, a known AMP-activated protein kinase (AMPK)-interacting protein that negatively regulates AMPK, a known activator of PGC-1a. Inhibition of Fnip1 reactivated AMPK/PGC-1a signaling and mitochondrial function in myocytes. Restoration of the expression of miR-499 in the mdx mouse model of Duchenne muscular dystrophy (DMD) reduced the severity of DMD. Thus, we have identified a miR-499/Fnip1/AMPK circuit that can serve as a mechanism to couple muscle fiber type and mitochondrial function. Keywords: muscle, contractile fiber type, mitochondrial function, microRNA, gene regulation RNA from three wild-type (non-transgenic (NTG)) and three miR-499 overexpressing (MCK-miR-499) mice was analyzed. three replicates of each are provided.
2016-09-03 | E-GEOD-72581 | biostudies-arrayexpress
Project description:Skeletal muscle atrophy is a serious and highly prevalent condition that remains poorly understood at the molecular level. Previous work found that skeletal muscle atrophy involves an increase in skeletal muscle Gadd45a expression, which is necessary and sufficient for skeletal muscle fiber atrophy. However, the direct mechanism by which Gadd45a promotes skeletal muscle atrophy was unknown. To address this question, we biochemically isolated skeletal muscle fiber proteins that associate with Gadd45a as it induces skeletal muscle atrophy in living mice. We found that Gadd45a interacts with multiple proteins in skeletal muscle fibers, including, most prominently, the MAP kinase kinase kinase MEKK4. Furthermore, by forming a complex with MEKK4 in skeletal muscle fibers, Gadd45a increases MEKK4 protein kinase activity, which is sufficient to induce skeletal muscle fiber atrophy and required for Gadd45a-mediated skeletal muscle fiber atrophy. Together, these results identify a direct biochemical mechanism by which Gadd45a induces skeletal muscle atrophy and provide new insight into way that skeletal muscle atrophy occurs at the molecular level.
2016-05-17 | MSV000079730 | MassIVE
Project description:The skeletal muscle growth and development is a very complicated but precisely regulated process with interwoven molecular mechanisms. Skeletal muscle is a very heterogeneous tissue that is made up of a large variety of functionally diverse fiber types. Muscle mass is therefore largely determined by the number and size of those fibres. These fibre characteristics are determined by hyperplasia before birth and by hypertrophy after. Around 65 dpc and three postnatal stages (newborn, 3 days; young, 60 days; and mature, 120 days) are key time points in swine skeletal muscle growth and development. We used microarrays to detail the global programme of gene expression underlying porcine skeletal muscle growth and development.
2011-07-01 | GSE24689 | GEO
Project description:Luchuan pig is a typical obese pig breed in China, and the diameter and area of its longissimus dorsi muscle fibers are significantly smaller than those of Duroc (lean) pig. Skeletal muscle fiber characteristics are related to meat quality of livestock. The smaller the diameter and area of muscle fiber, the better the meat quality. The diameter and area of muscle fibers are related to muscle growth and development. Therefore, we used the assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA sequencing (RNA-seq) analysis to investigate the potential mechanism underlying the difference in skeletal muscle growth and development between the two types of pigs. First, transposase-accessible chromatin was analyzed to map the landscape of open chromatin regions and transcription factor binding sites. We identified several transcription factors that potentially affected muscle growth and development, including TFAP4, MAX, NHLH1, FRX5, and TGIF1. We also found that transcription factors with basic helix-loop-helix structures had a preference for binding to genes involved in muscle development. Then, by integrating ATAC-seq and RNA-seq, we found that the Wnt signaling pathway, the mTOR signaling pathway, and other classical pathways regulate skeletal muscle development. In addition, we found some pathways that might regulate skeletal muscle growth, such as parathyroid hormone synthesis, secretion, and action, synthesis and degradation of ketone bodies, and the thyroid hormone signaling pathway, which were significantly enriched. After further study, we identified a number of candidate genes (ASNS, CARNS1, G0S2, PPP1R14C, and SH3BP5) that might be associated with muscle development. We also found that the differential regulation of chromatin openness at the level of some genes was contrary to the differential regulation at the level of transcription, suggesting that transcription factors and transcriptional repressors may be involved in the regulation of gene expression. Our study provided an in-depth understanding of the mechanism behind the differences in muscle fibers from two species of pig and provided an important foundation for further research on improving the quality of pork.
2021-07-29 | GSE180840 | GEO
Project description:The size of skeletal muscles, like that of all cells, is precisely regulated by intracellular signaling networks that determine the balance between overall rates of protein synthesis and degradation. Muscle fiber growth and protein synthesis are stimulated by the IGF1/Akt/mTOR pathway, and muscle wasting, as occurs with disuse, denervation, fasting, and various systemic diseases (e.g. cancer, sepsis) results from excessive protein breakdown in muscle and induction of a set of atrophy-related genes by the FoxO transcription factors. Here we show that the transcription factor JunB is also a major regulator of growth and atrophy of adult (post mitotic) muscle cells. We found that in atrophying myotubes, JunB protein was excluded from the nucleus and that decreasing JunB expression by RNAi in muscles of adults reduced fiber size. Furthermore, in normal muscles of adult mice JunB over-expression increased fiber diameter dramatically (up to 40% in 7 days), and stimulated protein synthesis, but unlike IGF-1 or insulin, JunB did not activate the Akt/mTOR pathway. Importantly, when JunB was transfected into denervated muscles to maintain its level high, fiber atrophy was prevented, and the induction of the critical atrophy-associated ubiquitin-ligases, atrogin-1 and MuRF-1, was greatly reduced. JunB inhibited their induction by impairing FoxO3 binding to their promoters and thus reduced the stimulation of protein breakdown by FoxO3. Thus JunB is important, not only in dividing populations, but also in mature skeletal muscle where it is required for the maintenance of muscle size and can induce rapid hypertrophy and block atrophy.
2010-01-01 | GSE18664 | GEO
Project description:Skeletal muscle excitation-contraction (EC) coupling is independent of calcium influx. In fact alternative splicing of the voltage-gated calcium channel CaV1.1 actively suppresses calcium currents in mature muscle. Why this might be necessary is not known. However, splicing defects causing aberrant expression of the calcium-conducting embryonic CaV1.1e splice variant correlate with muscle weakness in myotonic dystrophy. Here we deleted CaV1.1 exon 29 in mice. The continued expression of CaV1.1e resulted in increased calcium influx during EC coupling and spontaneous calcium sparks. While overall motor performance was normal, muscle force was reduced, endurance enhanced, and the fiber type composition shifted toward slower fibers. In contrast, oxidative enzyme activity and the mitochondrial content declined. Together with the dysregulation of key regulators of the slow program these findings indicate that limiting calcium influx during skeletal muscle EC coupling is important for the calcium signalâs secondary function in the activity-dependent regulation of fiber type composition. Differential gene expression between soleus and EDL muscle fibres from wildtype and Cav1.1 delta E29 mice.
2016-04-01 | E-GEOD-67803 | biostudies-arrayexpress