Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA109439 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Myostatin (GDF8) is a member of the TGF-beta family of proteins which is predominantly expressed in skeletal muscle and acts as a negative regulator of muscle mass. Inhibition of myostatin leads to muscle hypertrophy and has been shown to mitigate insulin resistance in mouse models of type 2 diabetes, although the mechanisms underlying this effect are unclear. We found that myostatin inhibition by AAV-mediated overexpression of the myostatin propeptide improves skeletal muscle insulin sensitivity in mice made insulin-resistant by high fat diet feeding. To gain insight into potential gene expression changes responsible for this effect, we performed microarray analysis on skeletal muscle samples from high fat diet-fed mice with and without myostatin inhibition.
2020-05-29 | GSE130622 | GEO
Project description:Skeletal muscle gene expression after myostatin knockout in mature mice
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Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from Mus musculus tissues (Heart, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
2021-05-05 | PXD022309 | Pride
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from seven Mus musculus tissues (Heart, Brain, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
2018-04-24 | PXD007288 | Pride
Project description:Myostatin inhibition prevents skeletal muscle pathophysiology in Huntington’s disease mice.
| PRJNA321381 | ENA
Project description:Skeletal muscle, the most abundant body’s tissue, plays vital roles in locomotion and metabolism. Myostatin is a negative regulator of skeletal muscle mass. In addition to increase muscle mass, Myostatin inhibition impacts on muscle contractility and energy metabolism. To decipher the mechanisms of action of the Myostatin inhibitors, we used proteomic and transcriptomic approaches to investigate the changes induced in skeletal muscles of transgenic mice overexpressing Follistatin, a physiological Myostatin inhibitor. Our proteomic workflow included a fractionation step to identify weakly expressed proteins and a comparison of fast versus slow muscles. Functional annotation of altered proteins supports the phenotypic changes induced by Myostatin inhibition, including modifications in energy metabolism, fiber type, insulin and calcium signaling, as well as membrane repair and regeneration. Less than 10% of the differentially expressed proteins were found to be also regulated at the mRNA level but the Biological Process annotation and the KEGG pathways analysis of transcriptomic results showed a great concordance with the proteomic data. Thus, this study describes the most extensive omics analysis of muscle overexpressing Follistatin, providing molecular-level insights to explain the observed muscle phenotypic changes
2017-08-17 | PXD005899 | Pride
Project description:We analyzed the functional role of DOR (Diabetes and Obesity Regulated gene) (also named Tp53inp2) in skeletal muscle. We show that DOR has a direct impact on skeletal muscle mass in vivo. Thus, using different transgenic mouse models, we demonstrate that while muscle-specific DOR gain-of-function results in reduced muscle mass, loss-of-function causes muscle hypertrophy. DOR has been described as a protein with two different functions, i.e., a nuclear coactivator and an autophagy regulator (Baumgartner et. al., PLoS One, 2007; Francis et. al., Curr Biol, 2010; Mauvezin et. al., EMBO Rep, 2010; Nowak et. al., Mol Biol Cell, 2009). This is why we decided to analyze which of these two functions could explain the phenotype observed in our mice models. In this regard, we performed a transcriptomic analysis using microarrays looking for genes differentially expressed in the quadriceps muscle of WT and SKM-Tg mice as well as in C and SKM-KO animals. Surprisingly, only a reduced number of genes were dysregulated upon DOR manipulation and most of the genes underwent mild changes in expression. These data strongly suggest that DOR does not operate as a nuclear co-factor in mouse skeletal muscle under the conditions subjected to study. In contrast, DOR enhances basal autophagy in skeletal muscle and promotes muscle wasting when autophagy is a contributor to muscle loss. To determine the functional role of DOR in skeletal muscle, we generated transgenic mice (SKM-Tg) overexpressing DOR specifically in skeletal muscle under the Myosin-Light Chain 1 promoter/enhancer. The open reading frame of DOR was introduced in an EcoRI site in the MDAF2 vector, which contains a 1.5 kb fragment of the MLC1 promoter and 0.9 kb fragment of the MLC1/3 gene containing a 3' muscle enhancer element (Rosenthal et. al., PNAS, 1989; Otaegui et. al., FASEB J, 2003). The fragment obtained after the digestion of this construct with BssHII was the one used to generate both transgenic mouse lines. Nontransgenic littermates were used as controls for the transgenic animals (Wt). In addition, a muscle-specific DOR knock-out mouse line (SKM-KO) was also generated by crossing homozygous DOR loxP/loxP mice with a mouse strain expressing Cre recombinase under the control of the Myosin-Light Chain 1 promoter (Bothe et. al., Genesis, 2000). Deletion of exons 3 and 4 driven by Cre recombinase caused the ablation of DOR expression. Non-expressing Cre DOR loxP/loxP littermates were used as controls for knockout animals (C). Four-month-old male mice were used in all experiments. Mice were in a C57BL/6J pure genetic background. We used microarrays to analyze the effect of DOR gain-of-function and DOR ablation on skeletal muscle gene expression Total RNA from quadriceps muscles from 4-month-old male mice was extracted and used for hibridization on Affimetrix microarrays
2014-02-13 | E-GEOD-54917 | biostudies-arrayexpress
Project description:We analyzed the functional role of DOR (Diabetes and Obesity Regulated gene) (also named Tp53inp2) in skeletal muscle. We show that DOR has a direct impact on skeletal muscle mass in vivo. Thus, using different transgenic mouse models, we demonstrate that while muscle-specific DOR gain-of-function results in reduced muscle mass, loss-of-function causes muscle hypertrophy. DOR has been described as a protein with two different functions, i.e., a nuclear coactivator and an autophagy regulator (Baumgartner et. al., PLoS One, 2007; Francis et. al., Curr Biol, 2010; Mauvezin et. al., EMBO Rep, 2010; Nowak et. al., Mol Biol Cell, 2009). This is why we decided to analyze which of these two functions could explain the phenotype observed in our mice models. In this regard, we performed a transcriptomic analysis using microarrays looking for genes differentially expressed in the quadriceps muscle of WT and SKM-Tg mice as well as in C and SKM-KO animals. Surprisingly, only a reduced number of genes were dysregulated upon DOR manipulation and most of the genes underwent mild changes in expression. These data strongly suggest that DOR does not operate as a nuclear co-factor in mouse skeletal muscle under the conditions subjected to study. In contrast, DOR enhances basal autophagy in skeletal muscle and promotes muscle wasting when autophagy is a contributor to muscle loss. To determine the functional role of DOR in skeletal muscle, we generated transgenic mice (SKM-Tg) overexpressing DOR specifically in skeletal muscle under the Myosin-Light Chain 1 promoter/enhancer. The open reading frame of DOR was introduced in an EcoRI site in the MDAF2 vector, which contains a 1.5 kb fragment of the MLC1 promoter and 0.9 kb fragment of the MLC1/3 gene containing a 3' muscle enhancer element (Rosenthal et. al., PNAS, 1989; Otaegui et. al., FASEB J, 2003). The fragment obtained after the digestion of this construct with BssHII was the one used to generate both transgenic mouse lines. Nontransgenic littermates were used as controls for the transgenic animals (Wt). In addition, a muscle-specific DOR knock-out mouse line (SKM-KO) was also generated by crossing homozygous DOR loxP/loxP mice with a mouse strain expressing Cre recombinase under the control of the Myosin-Light Chain 1 promoter (Bothe et. al., Genesis, 2000). Deletion of exons 3 and 4 driven by Cre recombinase caused the ablation of DOR expression. Non-expressing Cre DOR loxP/loxP littermates were used as controls for knockout animals (C). Four-month-old male mice were used in all experiments. Mice were in a C57BL/6J pure genetic background.
2014-02-13 | GSE54917 | GEO
Project description:Among the physiological consequences of extended space flight are loss of skeletal muscle and bone mass. One signaling pathway that plays an important role in maintaining muscle and bone homeostasis is that regulated by the secreted signaling proteins, myostatin and activin A. Here, we used both pharmacological and genetic approaches to investigate the effect of targeting myostatin/activin A signaling in mice that were sent to the International Space Station. We show that inhibition of myostatin/activin A signaling has a significant protective effect against microgravity-induced muscle and bone loss. These findings have implications for therapeutic strategies to combat the concomitant muscle and bone loss occurring in people afflicted with disuse atrophy on Earth as well as in astronauts in space, especially during prolonged missions.
2020-09-16 | GSE156321 | GEO
Project description:This study was to compare the gene expression of our anti-GDF8 (i.e. anti-myostatin) and anti-activin A antibody combination to that of the activin receptor type IIB (ActRIIB.hFc) trap in SCID mice. The study was conducted in tibialis anterior muscle that is a common muscle type for the hypertrophy study. The combination treatment produces very similar muscle growth in tibialis muscle as the ActRIIB.hFc trap, however our combination blocks two specific ligands compared to the many ligands the receptor trap will inhibit. The difference in gene expression between these groups demonstrates that despite producing similar muscle growth, the trap affecting more genes in muscle without producing additional muscle hypertrophy.
2017-06-01 | E-MTAB-4943 | biostudies-arrayexpress