Microarray analysis of transgenic mice specifically overexpressing FOXO1 in skeletal muscle (FOXO1 Tg mice)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE146919 | GEO | 2020/07/07
REPOSITORIES: GEO
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Project description:Microarray analysis of transgenic mice specifically overexpressing FOXO1 in skeletal muscle (FOXO1 Tg mice)
| PRJNA612433 | ENA
Project description:Skeletal muscle atrophy is one of the critical issues which elderly people face. The precise mechanism underlying muscle atrophy during aging is not fully understood. In order to identify miRNA whose expression is changed in age-associated muscle atrophy, we performed miRNA expression profiling of skeletal muscles in young and aged rats. Microarray analysis revealed differential miRNA expression in EDL and soleus muscles of aged rats compared with those of young rats. We next investigated whether the age-associated changes of miRNA expression observed in rats were recapitulated in mice and found that the expression level of miR-206 in EDL muscle and that of miR-196a in EDL and soleus muscles were respectively higher and lower in aged rodents than in young rodents. In mouse C2C12 myoblasts and myotubes, introduction of miR-196a decreased the protein level of Forkhead-box transcription factor Foxo1, a known target of miR-196a, indicating that miR-196a may regulate Foxo1 expression also in skeletal muscles. Furthermore, miR-196a overexpression exacerbated cell death caused by an exposure to hydrogen peroxide. Lastly, we demonstrated that expression of Foxo1 was elevated in EDL and soleus muscles of aged mice compared with those of young mice. These results suggest that miRNAs are involved in skeletal muscle atrophy during aging and that decreased miR-196a expression may protect skeletal muscle cells from oxidative stress in part through induction of Foxo1.
2016-08-31 | GSE70990 | GEO
Project description:Muscle denervation causes skeletal muscle atrophy. The goal of these studies was to determine the effects of denervation on skeletal muscle mRNA levels in C57BL/6 mice. For additional details see Ebert et al, Stress-Induced Skeletal Muscle Gadd45a Expression Reprograms Myonuclei and Causes Muscle Atrophy. JBC epub. June 12, 2012. Left sciatic nerves of C57BL/6 mice were transected. Seven days later bilateral tibialis anterior muscles were harvested. mRNA levels in denervated muscles were normalized to levels in contralateral innervated muscles.
2012-09-15 | E-GEOD-39195 | biostudies-arrayexpress
Project description:Skeletal muscle wasting is a devastating consequence of cancer that affects up to 80% of cancer patients and associates with reduced survival. Herein we identified the transcriptional repressor protein, Forkhead box P1 (FoxP1), as a downstream target gene of FoxO1 whose skeletal muscle expression is elevated in multiple models of cancer cachexia and in patients with cancer who exhibit cachexia. Through generation of inducible skeletal muscle-specific FoxP1 over-expressing (FoxP1iSkmTg/Tg) mice, we demonstrate that FoxP1 upregulation is sufficient to induce features of cachexia, including body and skeletal muscle wasting characterized by reduced muscle fiber cross-sectional area of type IIX/B muscle fibers. Muscles from FoxP1iSkmTg/Tg mice also showed significant muscle damage and myopathy characterized by the accumulation of p62 and cellular material-filled vesicles, the presence of centrally nucleated myofibers, and were significantly weaker than controls. In the context of cancer cachexia, blocking FoxP1 upregulation prevented the cancer-induced repression of target genes critical to muscle structural integrity and repair, including Myocyte enhancer factor 2c (Mef2c), improved muscle ultrastructure and significantly attenuated muscle fiber atrophy. We further show that the muscle wasting phenotype induced by FoxP1 required the activity of histone deacetylase (HDAC) proteins, which are well-established to cooperate with FoxP1 to mediate gene repression, and which were necessary for FoxP1-dependent repression of Mef2c. In summary, we identify FoxP1 as a negative transcriptional regulator of skeletal muscle mass and function, whose up-regulation mediates cancer-induced muscle wasting. We used microarrays to investigate the genome-wide transcriptional networks regulated by the FoxO1 and FoxP1 transcription factors in skeletal muscle of tumor-bearing mice.
2021-04-28 | GSE153068 | GEO
Project description:ATF4 is a fasting-induced trascription factor that promotes skeletal muscle atrophy. The goal of these studies was to determine how of loss of ATF4 affects skeletal muscle mRNA expression. For additional details see Ebert et al, Stress-Induced Skeletal Muscle Gadd45a Expression Reprograms Myonuclei and Causes Muscle Atrophy. JBC epub. June 12, 2012. Muscle-specfic ATF4 knockout (ATF4 mKO) mice and littermate controls were fasted for 24 hours and then tibialis anterior muscles were harvested. mRNA levels in ATF4 mKO muscles were normalized to levels in littermate control muscles.
2012-09-15 | E-GEOD-39193 | biostudies-arrayexpress
Project description:Gadd45a is a stress-induced protein that causes skeletal muscle atrophy. The goal of these studies was to determine the effects of Gadd45a overexpression on mRNA levels in mouse skeletal muscle. For additional details see Ebert et al, Stress-Induced Skeletal Muscle Gadd45a Expression Reprograms Myonuclei and Causes Muscle Atrophy. JBC epub. June 12, 2012. Tibialis anterior (TA) muscles from muscle-specfic ATF4 knockout mice (ATF4 mKO) were transfected with either 20 mg empty plasmid (pcDNA3) (left TA) or 20 mg pCMV-FLAG-Gadd45a (right TA) and harvested 7 days later. mRNA levels in Gadd45a-transfected muscles were normalized to levels in control transfected muscles.
2012-09-15 | E-GEOD-39196 | biostudies-arrayexpress
Project description:p53 regulates a distinct subset of skeletal muscle mRNAs during immobilization-induced skeletal muscle atrophy For additional details see Fox et al, p53 and ATF4 mediate distinct and additive pathways to skeletal muscle atrophy during limb immobilization. Am J Physiol Endocrinol Metab. 2014 Aug 1;307(3):E245-61. Bilateral tibialis anterior muscles were harvested at three days for the following conditions: 1) hindlimb immobilization of C57BL/6 mice; 2) hindlimb immobilization of p53 mKO and littermate control mice; 3) transfection of wild type mice with p53 plasmid or control plasmid
2014-11-05 | E-GEOD-62897 | biostudies-arrayexpress
Project description:DJ-1 is a causative gene for a familial form of Parkinson disease. DJ-1 deficient mice develop progressive behavioral abnormalities in gaits and forearm grip strength are hypoactive. The mechanisms under the activity are not fully known. Here we show that DJ-1 is critical for disuse- induced skeletal muscle atrophy. Firstly, DJ-1 expression is positively correlated with muscle mass in human, and is decreased in atrophy muscle of immobilization mice and aged human. Secondly, DJ-1-deficient muscles are dystrophic, as well as impaired in activities and oxidative capacity. In disuse-atrophic condition, skeletal muscle specific-DJ-1 knockout mice show less cross section area (CSA) and more central nuclei than control mice. Thirdly, biochemical analysis indicates that these changes are due to enhanced activation of FoxO1, and subsequent upregulation of atrogenes. Finally, the inhibitor of DJ-1, compound 23, can mimic the effects of DJ-1 ablation in vivo. Our results illuminate that skeletal muscle DJ-1 has an unexpected role in the regulation of catabolic signals from mechanical stimulation, providing a therapeutic target for muscle-wasting diseases.
2023-12-12 | GSE216408 | GEO
Project description:For additional details see Ebert et al, Identification and Small Molecule Inhibition of an ATF4-dependent Pathway to Age-related Skeletal Muscle Weakness and Atrophy. Quadriceps femoris muscles were harvested from 22-month-old muscle-specfic ATF4 knockout (ATF4 mKO) mice and littermate controls. mRNA levels in ATF4 mKO muscles were normalized to levels in littermate control muscles.
2015-09-03 | E-GEOD-72658 | biostudies-arrayexpress
Project description:In skeletal muscle, the pattern of electrical activity regulates the expression of proteins involved in synaptic transmission, contraction and metabolism. Disruptions in electrical activity, resulting from prolonged bed-rest, cast-immobilization or trauma, inevitably lead to muscle atrophy. The mechanisms that regulate muscle atrophy are poorly understood, but it seems likely that changes in gene expression play a key role in initiating and maintaining a muscle atrophy program. Previously, we found that Runx1, a transcription factor previously termed AML1, was substantially induced in muscle following denervation. More recently, we sought to determine whether this increase in Runx1 expression may be causally related to the morphological changes in skeletal muscle that accompany muscle disuse, notably muscle atrophy. We found that Runx1 is indeed required to sustain muscle and to minimize atrophy following denervation. Experiments described here are designed to identify the genes that are regulated by Runx1 in skeletal muscle with the particular goal of identifying genes that regulate muscle atrophy. We propose to use microarray analysis to identify genes, expressed in skeletal muscle, that are mis-regulated in mice lacking Runx1. We inactivated runx1 selectively in skeletal muscle and found that denervated myofibers in mutant mice atrophy far more (90% atrophy) than in wild-type mice (30% atrophy). We therefore reason that Runx1 activates and/or represses genes that are required to sustain muscle and to minimize atrophy. We generated MCK::cre; runx1f/- and runx1f/- control mice. In normal mice, an increase in runx1 expression is detected by two days after denervation and is maximal by five days after denervation. Muscle atrophy is first evident between one and two weeks after denervation. As we wish to avoid detecting global changes in gene expression that are associated with late stages of muscle atrophy, we plan to denervate muscle for three or five days and to compare gene expression in dissected innervated and denervated muscles from mutant and control mice. We will generate thirty samples for comparison-5 replicates per condition: Samples 1-3 from runx1f/- control mice. (1) innervated tibialis anterior muscles (TA); (2) 3-day-denervated TA; (3) 5-day-denervated TA. Samples 4-6 from MCK::cre; runx1f/- mice. (4) innervated TA; (5) 3-day-denervated TA; (6) 5-day-denervated TA. We obtain sufficient total RNA (10 micrograms) from each dissected muscle to avoid pooling samples. We will analyze adult mice of the same age (~six weeks after birth; most will be littermates) and sex-male. It is difficult to anticipate how many genes will be identified in this screen, as few target genes for Runx1 have been identified in any cell type and none in skeletal muscle. Moreover, although we would prefer to focus our attention on genes that are strongly dependent upon Runx1 expression (e.g. more than 5-fold difference in expression in wild-type and mutant mice), we do not know the extent to which target gene expression will depend upon Runx1. For these reasons, in these experiments, we will analyze expression from five âidenticalâ samples, so that we can be confident that even small (e.g. three-fold) differences in expression can be reliably determined. Importantly, in order to confirm results obtained from the microarray data, we will use other assays (RNase protection) to measure RNA expression of candidate genes in innervated and denervated muscles of wild-type and mutant mice.
2008-06-13 | E-GEOD-4411 | biostudies-arrayexpress