Influence of hyperthyroid conditions on gene expression in rat extraocular muscles
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE13414 | GEO | 2009/03/06
SECONDARY ACCESSION(S): PRJNA113985
REPOSITORIES: GEO
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Project description:Extraocular muscles (EOMs) are a highly specialized type of tissue with a wide range of unique properties, including characteristic innervation, development, and structural proteins. Even though EOMs are frequently and prominently involved in thyroid-associated diseases, little is known about the immediate effects of thyroid hormone on these muscles. In order to create a comprehensive profile of changes in gene expression levels in EOMs induced by thyroid hormone, hyperthyroid conditions were simulated by treating adult Sprague-Dawley rats with intraperitoneal injections of 25 μg T3 per 100 g body weight over the course of six weeks; subsequently, microarray analysis was used to determine changes in mRNA levels in EOMs from T3-treated animals relative to untreated controls. Adult Sprague-Dawley rats (initial body weight 200 ± 40 g) were fed ad libitum with standard laboratory diet and tap water. Eight rats were randomly divided into a T3-treated and a control group. To simulate a chronically hyperthyroid state, T3 treatment was administered by intraperitoneal injections of 25 µg T3 (Sigma-Aldrich) per 100 g body weight. Injections were administered every second day over a period of six weeks. 24 hours after the last injection, the animals were sacrificed by CO2 asphyxiation. For RNA isolation, the extraocular muscles (EOMs) were removed, flash-frozen in liquid nitrogen and stored at -80 °C until further use.
2009-03-06 | E-GEOD-13414 | biostudies-arrayexpress
Project description:Extraocular muscles (EOMs) are a highly specialized type of tissue with a wide range of unique properties, including characteristic innervation, development, and structural proteins. Even though EOMs are frequently and prominently involved in thyroid-associated diseases, little is known about the immediate effects of thyroid hormone on these muscles. In order to create a comprehensive profile of changes in gene expression levels in EOMs induced by thyroid hormone, hyperthyroid conditions were simulated by treating adult Sprague-Dawley rats with intraperitoneal injections of 25 μg T3 per 100 g body weight over the course of six weeks; subsequently, microarray analysis was used to determine changes in mRNA levels in EOMs from T3-treated animals relative to untreated controls. RNA isolated from tibialis anterior muscles of the same animals was used as a reference fast-twitch muscle.
2009-03-06 | GSE13413 | GEO
Project description:Extraocular muscles (EOMs) are a highly specialized type of tissue with a wide range of unique properties, including characteristic innervation, development, and structural proteins. Even though EOMs are frequently and prominently involved in thyroid-associated diseases, little is known about the immediate effects of thyroid hormone on these muscles. In order to create a comprehensive profile of changes in gene expression levels in EOMs induced by thyroid hormone, hyperthyroid conditions were simulated by treating adult Sprague-Dawley rats with intraperitoneal injections of 25 ?g T3 per 100 g body weight over the course of six weeks; subsequently, microarray analysis was used to determine changes in mRNA levels in EOMs from T3-treated animals relative to untreated controls. RNA isolated from tibialis anterior muscles of the same animals was used as a reference fast-twitch muscle. Adult Sprague-Dawley rats (initial body weight 200 ± 40 g) were fed ad libitum with standard laboratory diet and tap water. Eight rats were randomly divided into a T3-treated and a control group, three males and one female each. To simulate a chronically hyperthyroid state, T3 treatment was administered by intraperitoneal injections of 25 µg T3 (Sigma-Aldrich, St. Louis, MO, U.S.A.) per 100 g body weight. Injections were administered every second day over a period of six weeks. 24 hours after the last injection, the animals were sacrificed by CO2 asphyxiation, muscles were dissected immediately after death. Each of the four biological replicates in each group was used for a single microarray each. RNA from EOMs was used. Tibialis anterior RNA from the same animals served as a fast-twitch reference muscle.
2009-03-06 | E-GEOD-13413 | biostudies-arrayexpress
Project description:Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disorder characterized by progressive weakness of almost all skeletal muscles, whereas extraocular muscles (EOMs) are comparatively spared. While hindlimb and diaphragm muscles of end-stage SOD1G93A (G93A) mice (a familial ALS mouse model) exhibit severe denervation and depletion of Pax7+satellite cells (SCs), we found that the pool of SCs and the integrity of neuromuscular junctions (NMJs) are maintained in EOMs. In cell sorting profiles, SCs derived from hindlimb and diaphragm muscles of G93A mice exhibit denervation-related activation, whereas SCs from EOMs of G93A mice display spontaneous (non-denervation-related) activation, similar to SCs from wild-type mice. Specifically, cultured EOM SCs contain more abundant transcripts of axon guidance molecules, including Cxcl12, along with more sustainable renewability than the diaphragm and hindlimb counterparts under differentiation pressure. In neuromuscular co-culture assays, AAV-delivery of Cxcl12 to G93A-hindlimb SC-derived myotubes enhances motor neuron axon extension and innervation, recapitulating the innervation capacity of EOM SC-derived myotubes. G93A mice fed with sodium butyrate (NaBu) supplementation exhibited less NMJ loss in hindlimb and diaphragm muscles. Additionally, SCs derived from G93A hindlimb and diaphragm muscles displayed elevated expression of Cxcl12 and improved renewability following NaBu treatment in vitro. Thus, the NaBu-induced transcriptomic changes resembling the patterns of EOM SCs may contribute to the beneficial effects observed in G93A mice. More broadly, the distinct transcriptomic profile of EOM SCs may offer novel therapeutic targets to slow progressive neuromuscular functional decay in ALS and provide possible ‘response biomarkers’ in pre-clinical and clinical studies.
2023-12-11 | GSE249484 | GEO
Project description:The fast and constant activity of the extraocular muscles (EOMs) impose mechanical and metabolic stresses not typically seen in limb skeletal muscles. These functional properties may explain why EOMs seem to age at a faster rate than other skeletal muscles. Using high-density cDNA microarrays, this study investigated the gene expression profile of EOMs and extensor digitorum longus muscles (EDL) of Fischer 344/Brown Norway F1 hybrid rats at 6-, 18- and 30-months of age. At 6-mo, 705 genes and expressed sequence tags (ESTs) were differentially expressed in EOMs (436 up, 269 down). Overall, the EOM profile at this age was mostly consistent with the increased expression of fetal, developmental and EOM-specific myosin isoforms, enzymes involved in glycolysis and TCA cycle, and ion transporters and pumps, confirming the notion that EOM may represent a distinct muscle group (PNAS 98:12062, 2001). Interestingly, at 18-mo only 36 probes were significantly different in EOM (15 up, 21 down), most of them ESTs. However, at 30-mo EOMs had 655 differentially expressed genes and ESTs (480 up, 175 down). In this age group, the EOM expression profile reverted to a pattern similar to that found at 6-mo, with evidence of ongoing tissue remodeling and increased expression of antioxidant enzymes. These results indicate that the gene expression profile of EOM and EDL evolve differently throughout the lifespan. Keywords: aging, muscle type comparison
2005-09-17 | GSE3309 | GEO
Project description:The extraocular muscles (EOMs) are a unique group of muscles that are anatomically and physiologically distinct from other skeletal muscles. Previously, we and others have shown that EOMs have a unique transcriptome and proteome. Here, we investigated the expression pattern of microRNAs (miRNAs) in EOM, as they may play a role in generating the unique EOM allotype. We screened LC Sciences miRNA microarrays covering the sequences of miRBase 10.0 to define the microRNAome of normal mouse EOM and tibialis anterior (TA) limb muscle. 74 miRNAs were found to be differentially regulated (p-value < 0.05) and 31 miRNAs (14 up-regulated and 17 down-regulated) were found to be differentially regulated at a signal strength > 500 including the muscle-specific miR-206, miR-1, miR-133a, miR-133b and miR-499. qPCR analysis was used to validate the differential expression. Bioinformatic tools were used to identify potential miRNA-mRNA-protein interactions and integrate data with previous transcriptome and proteomic profiling data. Luciferase assays using co-transfection of precursor miRNAs (pre-miRNAs) along with reporter constructs containing the 3’-untranslated region (3’UTR) of their predicted target genes were used to validate targeting by identified miRNAs. The definition of the EOM microRNAome complements existing transcriptome and proteome data about the molecular make-up of EOM and provides further insight into regulation of muscle genes. These data will also help to further explain the unique EOM muscle allotype and its differential sensitivity to diseases such as Duchenne's muscular dystrophy (DMD) and may assist in development of therapeutic strategies.
2009-12-15 | GSE18538 | GEO
Project description:The extraocular muscles (EOMs) are a unique group of muscles that are anatomically and physiologically distinct from other skeletal muscles. Previously, we and others have shown that EOMs have a unique transcriptome and proteome. Here, we investigated the expression pattern of microRNAs (miRNAs) in EOM, as they may play a role in generating the unique EOM allotype. We screened LC Sciences miRNA microarrays covering the sequences of miRBase 10.0 to define the microRNAome of normal mouse EOM and tibialis anterior (TA) limb muscle. 74 miRNAs were found to be differentially regulated (p-value < 0.05) and 31 miRNAs (14 up-regulated and 17 down-regulated) were found to be differentially regulated at a signal strength > 500 including the muscle-specific miR-206, miR-1, miR-133a, miR-133b and miR-499. qPCR analysis was used to validate the differential expression. Bioinformatic tools were used to identify potential miRNA-mRNA-protein interactions and integrate data with previous transcriptome and proteomic profiling data. Luciferase assays using co-transfection of precursor miRNAs (pre-miRNAs) along with reporter constructs containing the 3â-untranslated region (3âUTR) of their predicted target genes were used to validate targeting by identified miRNAs. The definition of the EOM microRNAome complements existing transcriptome and proteome data about the molecular make-up of EOM and provides further insight into regulation of muscle genes. These data will also help to further explain the unique EOM muscle allotype and its differential sensitivity to diseases such as Duchenne's muscular dystrophy (DMD) and may assist in development of therapeutic strategies. Total RNA from four EOM and four TA tissue samples dissected from four adult male C57/Bl10 mice were used (TA served as control) to screen four LC Sciences microRNA Microarray chips. The chips contained microRNA sequences based on miRBase content 10.0 totalling 568 different miRNAs. Samples were labelled with Cy3 and Cy5 using dye-swap. Relative differences of miRNA expression was expressed as fold-changes EOM/TA, which were calculated after normalization across all four arrays.
2010-05-18 | E-GEOD-18538 | biostudies-arrayexpress
Project description:Human strabismic extraocular muscles (EOMs) differ from normal EOMs in structural and functional properties, but the gene expression profile of these two types of human EOM has not been examined. Differences in gene expression may inform about causes and effects of the strabismic condition in humans. Our samples are from human strabismic patients undergoing corrective surgery, and from human organ donors with no history of EOM disease. Microarray analysis showed that 604 genes in these samples have significantly different expression. Expression was predominantly up-regulated in genes involved in extracellular matrix structure and down-regulated in genes related to contractility.
2012-08-14 | GSE38780 | GEO
Project description:Extraocular Muscle is Defined by a Fundamentally Distinct Gene Expression Profile. Adult mouse extraocular, masticatory, and hindlimb (gastrocnemius/soleus) muscles of adult mice were compared using Affymetrix microarrays. Data form part of publication: Proceedings of the National Academy of Sciences USA 98:12062-12067, 2001. Keywords: parallel sample
2004-02-27 | GSE1062 | GEO
Project description:Human strabismic extraocular muscles (EOMs) differ from normal EOMs in structural and functional properties, but the gene expression profile of these two types of human EOM has not been examined. Differences in gene expression may inform about causes and effects of the strabismic condition in humans. Our samples are from human strabismic patients undergoing corrective surgery, and from human organ donors with no history of EOM disease. Microarray analysis showed that 604 genes in these samples have significantly different expression. Expression was predominantly up-regulated in genes involved in extracellular matrix structure and down-regulated in genes related to contractility. We used four normal samples and four strabismic samples. Three normal samples were from independent donors. One normal sample was a different piece of the same EOM from one of the 3 donors. All four strabismic samples were independent samples.
2012-08-13 | E-GEOD-38780 | biostudies-arrayexpress