Project description:Sarcopenia is the age-induced, progressive loss of skeletal muscle mass and function, which is accompanied by reduced muscle performance. Individuals with sarcopenia often become bedridden or dependent on a wheelchair, leading to decreased quality of life. In this study, to better understand changes in skeletal muscle during sarcopenia, we performed a microarray analysis of skeletal muscle in young (13-week-old) and aged (26-month-old) mice. The microarray data shows that expression of the enzymes related to glucose and polyamine metabolism were decreased in aged mice compared with young mice.
Project description:FOXO1, a member of the FOXO forkhead type transcription factors, is markedly up-regulated in skeletal muscle during atrophy. Previously, we created transgenic mice specifically overexpressing FOXO1 in skeletal muscle (FOXO1 Tg mice). These mice weighed less than the wildtype control mice, had a reduced skeletal muscle mass. In this study, to better understand changes in skeletal muscle during atrophy, we performed a microarray analysis of skeletal muscle in wild-type control and FOXO1 Tg mice. The microarray data shows that in the skeletal muscles of FOXO1 Tg mice, gene expression of PGC-1β, a transcriptional regulator whose increased expression activates energy-expenditure-related genes in skeletal muscles, is decreased.
Project description:DNA methylation occurs as 5-methylcytosines mainly at cytosine-guanine dinucleotides, so-called CpG sites, and such methylation is a well-studied epigenetic mechanism for transcriptional regulation. Generally, DNA methylation of the gene promoter is correlated with transcriptional repression. Genomic DNA methylation patterns are established by the actions of the de novo methyltransferases Dnmt3a and Dnmt3b, and are maintained by the methyltransferase Dnmt1. Expression of Dnmt3a mRNA is relatively high in skeletal muscle, suggesting a major role in transcriptional regulation. Also, denervation of skeletal muscle decreased expression of Dnmt3a mRNA, suggesting involvement of Dnmt3a in pathophysiology during atrophy. Decreased regeneration capacity in atrophied skeletal muscle hampers muscle mass recovery after injury and the impaired muscle function, lowers the quality of life. We found that in skeletal muscle of atrophy models, Dnmt3a was decreased. Muscle regeneration was delayed in the skeletal muscle-specific Dnmt3a knockout (Dnmt3a-KO) mice, in which Dnmt3a was deleted in skeletal muscle as well as in satellite cells, important for muscle regeneration. In this study, we used Dnmt3a-KO mice, and attempt to clarify the mechanism of reduced muscle regeneration during atrophy. The microarray data shows that expression of a Gdf/Bmp family protein Gdf5, which suppressed differentiation of satellite cells, is activated in Dnmt3a-KO mice compared with wild-type mice.
Project description:Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC1α) is a coactivator of various nuclear receptors and other transcription factors that shows increased expression in skeletal muscle during exercise. In skeletal muscle, PGC1α is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellular signaling, and transcriptional responses. Several isoforms of PGC1α mRNA have recently been identified. PGC1α-a is a full-length isoform of PGC1α that was the first to be isolated. PGC1α-b is another isoform of PGC1α, which is considered to be similar in function to PGC1α-a, differing by only 16 amino acids at the amino terminus. We have previously generated independent lines of transgenic mice that overexpress PGC1α-a or PGC1α-b in skeletal muscle. The microarray data shows that energy metabolism-related pathways such as the TCA cycle, branched-chain amino acid metabolism, purine nucleotide pathway, and malate–aspartate shuttle are activated in PGC1α transgenic mice compared with wild-type mice.
Project description:We generated a tamoxifen-inducible skeletal muscle-specific Bmal1 knockout mouse model and performed a time-course microarray experiment to identify gene expression changes downstream of the molecular clock. We report the transcrpt expression profiles in adult gastrocnemius skeletal muscle harvested from iMS-Bmal1-/- and at 4 hour intervals for a full circadian time-course (6 time-points).
Project description:Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC1α) is a coactivator of various nuclear receptors and other transcription factors that shows increased expression in skeletal muscle during exercise. In skeletal muscle, PGC1α is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellular signaling, and transcriptional responses. Several isoforms of PGC1α mRNA have recently been identified. PGC1α-a is a full-length isoform of PGC1α that was the first to be isolated. PGC1α-b is another isoform of PGC1α, which is considered to be similar in function to PGC1α-a, differing by only 16 amino acids at the amino terminus. We have previously generated independent lines of transgenic mice that overexpress PGC1α-a or PGC1α-b in skeletal muscle. The microarray data shows that energy metabolism-related pathways such as the TCA cycle, branched-chain amino acid metabolism, purine nucleotide pathway, and malate–aspartate shuttle are activated in PGC1α transgenic mice compared with wild-type mice. For microarray analysis, RNA was isolated from the gastrocnemius skeletal muscle of wild-type control mice (12 weeks of age) as well as transgenic mice [PGC1α-a (E) (Miura et al., J. Biol. Chem. 278:31385-90, 2003), 12 weeks of age; PGC1α-b (02-1) (Miura et al., Endocrinology 149:4527-33, 2008), 14 weeks of age; and PGC1α-b (03-2) (Miura et al., Endocrinology 2008), 14 weeks of age]. Samples from wild-type and transgenic mice (N = 5 for each group) were pooled before use.
Project description:RNA-seq was performed to investigate the role of Rrm2b in skeletal muscle. Type II skeletal muscle fibers were collected from wild-type (C57BL/6) mice and two Rrm2b knockout models, the skeletal muscle-specific knockout (Rrm2b F/F;HSA-Cre, smKO) and satellite cell-specific knockout (Rrm2b F/F;Pax7-CreERT2, scKO).