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Gene expression analysis in skeletal muscle and heart of 11 days-old TK2 knockout mice

ABSTRACT: TK2 deficiency causes severe mtDNA depeltion in several tissues, including skeletal muscle and heart. TK2 knockout mice grow slower and their skeletal muscles appeared significantly underdeveloped, whereas heart was close to normal size. We used microarrays in order to compare the transcriptomes in skeletal muscle and heart tissue of 11 days-old TK2 knockout pups with the sames tissues of wild-type pups at the same age.

ORGANISM(S): Mus musculus

PROVIDER: GSE38449 | GEO | 2012/07/31

SECONDARY ACCESSION(S): PRJNA167961

REPOSITORIES: GEO

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Gene expression analysis in skeletal muscle and heart of 11 days-old TK2 knockout mice

Project description:TK2 deficiency causes severe mtDNA depeltion in several tissues, including skeletal muscle and heart. TK2 knockout mice grow slower and their skeletal muscles appeared significantly underdeveloped, whereas heart was close to normal size. We used microarrays in order to compare the transcriptomes in skeletal muscle and heart tissue of 11 days-old TK2 knockout pups with the sames tissues of wild-type pups at the same age. We collected skeletal muscle from the hind limb and hearts of three 11 days-old TK2 knockout and three wild-type pups and extracted total RNA. These RNA samples were used for hybridization in Affymetrix arrays.

2012-07-30 | E-GEOD-38449 | biostudies-arrayexpress

High levels of TFAM repress in vivo transcription of mitochondrial DNA

Project description:Mammalian mitochondrial DNA (mtDNA) is coated with mitochondrial transcription factor A (TFAM) and compacted into nucleoids. TFAM is not only the main component of mitochondrial nucleoids but its levels can also control mtDNA copy number. Here we show that the TFAM-to-mtDNA ratio is critical for maintaining normal mtDNA expression in different tissues of the mouse. BAC transgenic mice with a 1.5-fold increase in TFAM protein levels maintain a normal TFAM-to-mtDNA ratio in different tissues and as a consequence mitochondrial gene expression, nucleoid distribution and whole animal metabolism are all unaltered. In contrast, mice expressing TFAM from the CAG promoter in the ROSA26 locus have 4.5-fold increase of TFAM protein levels in heart and skeletal muscle and develop pathology leading to early postnatal lethality. The TFAM-to-mtDNA ratio varies widely between tissues in these mice and is very high in skeletal muscle where it causes strong repression of mtDNA expression and deficient oxidative phosphorylation (OXPHOS) despite normal mtDNA levels. In heart, mtDNA copy number is increased leading to a near normal TFAM-to-mtDNA ratio and maintained OXPHOS capacity. In the liver, mtDNA expression is maintained despite increased TFAM levels and normal mtDNA levels. Here, tissue-specific induction of the LONP1 protease and mitochondrial RNA polymerase (POLRMT) expression counteracts the silencing effect of high TFAM levels. We conclude that the TFAM-to-mtDNA ratio has an important role in maintaining mtDNA expression in vivo. TFAM acts as a general repressor of mtDNA expression and this effect can be counterbalance by tissue-specific expression of regulatory factors.

2021-08-18 | PXD023050 | Pride

Expression data from POLG1 patients and control subjects muscle

Project description:Pathogenic mutations in the catalytic DNA polymerase gamma (POLG1) gene result in the accumulation of mtDNA mutations, deletions and/or decrease of mtDNA copy number. These features interfere with proper functioning of the electron transport chain, mostly affecting metabolically active tissues such as the brain, the heart and the liver. So far, mechanisms underlying POLG pathogenesis are not fully understood. To identify general pathways influenced by mutant polymerase gamma, skeletal muscle gene expression profiles of six POLG1 patients and twelve controls were compared. Patient and control subject from three age categories (<10; 11-49; >50) were selected. RNA was extracted from skeletal muscle biopsies and hybridized on Affymetrix microarrays.

2016-07-03 | E-GEOD-18715 | biostudies-arrayexpress

cDNA microarray expression data of heart, skeletal muscle and liver comparing Irf2bp2-null mice to wild type controls

Project description:Interferon regulatory factor 2 binding protein 2 (Irf2bp2), a co-repressor of Irf2, is required for fetal hepatic erythropoiesis through the expansion of erythromyeloid progenitors. Mice with germline ablation of the entire Irf2bp2 transcript produced no viable Irf2bp2-null (knockout, KO) pups in first litters. In subsequent litters, fewer than 1/3 of the expected KO pups were born and half survived to adulthood. Heart, skeletal muscle and liver tissues (tissues with high Irf2bp2 expression) were acquired from WT and KO mice, followed by RNA extraction using the RNeasy Midi Kit and subsequent gene expression profiling using the Affymetrix Mouse Gene 1.0 ST v1 array. Transcriptome profiles of surviving KO mice were contrasted to WT mice giving insight to modified gene expression in the absence of Irf2bp2 across multiple vital tissues.

2023-02-02 | E-MTAB-11558 | biostudies-arrayexpress

Heteroplasmy between wild type mitochondrial DNA variants is detrimental and shorten life span

Project description:We evaluated here the physiological consequences of the generation of heteroplasmic embryos by mix of two wild type mtDNAs in the same zygote. In this animal model, mtDNA heteroplasmy is actively combated during germ-line transmission, embryonic development and somatic life of most differentiated cells. mtDNA heteroplasmy alone, even when both mtDNA types are individually non-pathogenic, causes a disease affecting mainly those tissues that are not able to reduce their heteroplasmy: heart, lung and skeletal muscle.

2020-01-01 | GSE93920 | GEO

Expression data from POLG1 patients and control subjects muscle

2016-01-01 | GSE18715 | GEO

Transcriptome changes in 11 organs after endogenous melatonin reduction

Project description:We knocked out the Aanat gene of mice by CRISPR CAS technology, and performed RNA-seq on brain, heart, liver, kidney, lung, skin, stomach, spleen, testis, skeletal muscle, and EWAT of 10-week-old wild-type(WT) and Aanat knockout(Aanat-/-) mice. Through the analysis of differentially expressed genes, we found the genes related to disease and tissue development. Finally, these differential genes were verified by qRT-PCR

2022-04-28 | GSE194203 | GEO

Tissue- and Pathway-Specific Metabolomic Profiles of the Steroid Receptor Coactivator (SRC) family

Project description:The rapidly growing family of coregulators of nuclear receptors includes coactivators that promote transcription and corepressors that harbor the opposing function. In recent years, coregulators have begun to emerge as important regulators of metabolic homeostasis, including the p160 Steroid Receptor Coactivator (SRC) family. Members of the SRC family have been ascribed important roles in control of gluconeogenesis in liver and fatty acid oxidation in skeletal muscle. To provide a deeper and more granular understanding of the metabolic impact of SRC family members, we have performed targeted metabolomics analysis of key metabolic byproducts of glucose, fatty acid, and amino acid metabolism in mice with global knockout of SRC-1, SRC-2, or SRC-3. We measured amino acids, acyl carnitines, and organic acids in five tissues with key metabolic functions (liver, heart, skeletal muscle, brain, plasma) isolated from SRC-1, -2, or -3 knockout mice and their wild-type littermates in the fed and fasted conditions, thereby unveiling unique metabolic functions of each SRC coactivator. Overall, we observed entire groups or subgroups of metabolites belonging to discrete metabolic pathways that were influenced in different tissues and/or feeding states due to ablation of individual SRC isoforms. Surprisingly, we identified very few metabolites that changed universally across the three SRC knockout models. These findings demonstrate that coactivator function has very limited redundancy even within the homologous SRC coactivator family. Furthermore, this work also demonstrates the use of metabolomics as a means for identifying novel metabolic regulatory functions of transcriptional coregulators.

2013-04-10 | MTBLS30 | MetaboLights

Proteomic characterization of the heart and skeletal muscle reveals widespread Arginine ADP-ribosylation by the ectopic ADP-ribosyltransferase ARTC1

Project description:ADP-ribosylation has thus far been studied on the proteomic level mainly in cell lines and in combination with genotoxic stress. The clostridium-like ADP-ribosyltransferases (i.e. ARTC) are GPI-anchored or secreted proteins that are expressed in a highly tissue specific manner. Transcriptomic data revealed that ARTC1 is expressed in skeletal muscle and heart tissue. Although ARTC1 is highly active in vitro, identification of ARTC1 targets in vivo and subsequent characterization of ARTC1-regulated cellular processes on the proteome level has been challenging and only a few ADP-ribosylated targets are known. Using a new MS-based workflow, we provide the thus far most extensive identification of endogenous ADP-ribosylomes with hundreds of ARTC1-ADP-ribosylated proteins in C2C12 myotubes and in skeletal muscle and heart tissues from wild type and newly generated ARTC1 knockout mice. These proteins are ADP-ribosylated on arginine residues and mainly located on the cell surface or in the extracellular space. They are associated with signal transduction, transmembrane transport and muscle function. Together we provide the first comprehensive systems-level analysis of endogenous ADP-ribosylation in two different muscle tissues revealing a widespread function of ARTC1 and its targets.

2018-08-17 | PXD008041 | Pride

Assessment of the response of aerobic and anaerobic muscle tissues of gilthead sea bream (Sparus aurata L.) to caloric restriction

Project description:Fish were fed from May to August (11 weeks) with a commercial diet (D-2 Excel 1P, Skretting, Stavanger, Norway) twice per day at two different feeding levels: full ration until visual satiety (MAX group), and maintenance ration (30% of the satiation level) (MANT group). The effect of ration size on aerobic (red skeletal muscle, heart) and anaerobic (white skeletal muscle) muscle tissue transcriptome was addressed by means of microarray analysis. The following tissues of animal from the MAX and MANT groups were analyzed: white skeletal muscle, red skeletal muscle and heart.

2014-07-09 | E-GEOD-47859 | biostudies-arrayexpress

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