Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Rhabdomyosarcomas in aging A/J mice

ABSTRACT: Rhabdomyosarcomas (RSCs) are skeletal muscle neoplasms found in humans and domestic mammals. The A/J inbred strain developed a high frequency of RSC by 20 months of age while BALB/cJ and BALB/cByJ also develop RSC but less frequently. These neoplasms affected skeletal muscle surrounding either the axial or proximal appendicular skeleton and were characterized by pleomorphic cells with abundant eosinophilic cytoplasm, multiple nuclei, and cross striations that invaded locally. The diagnosis was confirmed by detection of alpha-sarcomeric actin and myogenin in the neoplastic cells using immunocytochemistry. The A/J strain, but not the related BALB/c substrains, is also characterised by a progressive muscular dystrophy homologous to limb-girdle muscular dystrophy type 2B. The association between the development of RSC in similar muscle groups to those most severely affected by the progressive muscular dystrophy suggested that these neoplasms developed from abnormal regeneration of the skeletal muscle exacerbated by the dysferlin mutation. Transcriptome analyses revealed marked downregulation of genes in muscular development and function signaling networks. Non-synonymous coding SNPs were found in Myl1, Abra, Sgca, Ttn, and Kcnj12 suggesting these may be important in the pathogenesis of RSC. These studies suggest that A strains of mice can be useful models for dissecting the molecular genetic basis for development, progression, and ultimately for testing novel anticancer therapeutic agents dealing with rhabdomyosarcoma.

ORGANISM(S): Mus musculus

PROVIDER: GSE29775 | GEO | 2011/08/01

SECONDARY ACCESSION(S): PRJNA141047

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Rhabdomyosarcomas in aging A/J mice

Project description:Rhabdomyosarcomas (RSCs) are skeletal muscle neoplasms found in humans and domestic mammals. The A/J inbred strain developed a high frequency of RSC by 20 months of age while BALB/cJ and BALB/cByJ also develop RSC but less frequently. These neoplasms affected skeletal muscle surrounding either the axial or proximal appendicular skeleton and were characterized by pleomorphic cells with abundant eosinophilic cytoplasm, multiple nuclei, and cross striations that invaded locally. The diagnosis was confirmed by detection of alpha-sarcomeric actin and myogenin in the neoplastic cells using immunocytochemistry. The A/J strain, but not the related BALB/c substrains, is also characterised by a progressive muscular dystrophy homologous to limb-girdle muscular dystrophy type 2B. The association between the development of RSC in similar muscle groups to those most severely affected by the progressive muscular dystrophy suggested that these neoplasms developed from abnormal regeneration of the skeletal muscle exacerbated by the dysferlin mutation. Transcriptome analyses revealed marked downregulation of genes in muscular development and function signaling networks. Non-synonymous coding SNPs were found in Myl1, Abra, Sgca, Ttn, and Kcnj12 suggesting these may be important in the pathogenesis of RSC. These studies suggest that A strains of mice can be useful models for dissecting the molecular genetic basis for development, progression, and ultimately for testing novel anticancer therapeutic agents dealing with rhabdomyosarcoma. Total RNA obtained from skeletal muscle samples from neoplastic and non-neoplastic tissues. Four rhabdomyosarcomas (~450 day old male A/J mice) and 8 nonneoplastic skeletal muscle samples (425-550 day old male A/J mice) were used

2011-07-31 | E-GEOD-29775 | biostudies-arrayexpress

Decoding the transcriptome of muscular dystrophy using single-nucleus RNA sequencing

Project description:Muscular dystrophy is a group of diseases that cause progressive weakness and degeneration of the skeletal muscles that control movement. Lacking polymerase I transcription release factor (PTRF, also known as Cavin1), an essential caveolae component, causes a secondary deficiency of caveolins resulting in muscular dystrophy. Because skeletal muscle is a heterogeneous tissue composed of different metabolic muscle fiber (myofibers) and mononuclear cells, the transcriptome responses of these myofibers and mononuclear cell to muscular dystrophy caused by PTRF deletion has not been explored. Here, we create muscular dystrophy mice caused by the deletion of PTRF gene and apply single-nucleus RNA sequencing (snRNA-seq) to unveil transcriptional changes in the skeletal muscle of mice with muscular dystrophy at single-nucleus resolution.

2023-05-31 | GSE217390 | GEO

Muscle from patients with mitochondrial myopathies and congenital muscular dystrophies versus normal human muscle

Project description:Global gene expression analysis was performed comparing human skeletal muscle samples from patients with various forms of muscular dystrophy and mitochondrial myopathies in order to identify specific gene expression changes associated with collagen VI deficiency (leading to UllrichM-BM-4s Congenital Muscular Dystrophy) and depletion of mitochondrial DNA relative to other mitochondrial myopathies We analysed the gene expression profile of skeletal muscle from children suffering from mitochondrial myopathies and various forms of muscular dystrophy relative to skeletal muscle from healthy children using commercially available arrays that represents the complete human genome (Agilent Human SurePrintGE, 8x60K )

2015-01-20 | E-GEOD-43698 | biostudies-arrayexpress

Expression profiling of FRG1 transgenic mice.

Project description:RNA from skeletal muscle of mice over-expressing selectively in the skeletal muscle the gene FRG1, a candidate of facioscapulohumeral muscular dystrophy, was compared to RNA from skeletal muscle of WT mice.

2013-09-04 | GSE28575 | GEO

Mechanisms associated with systemic effects of cancer

Project description:Cancer is considered as a disease of a specific organ, but its effects are felt throughout the body. The systemic effects of cancer can lead to weakness in muscles and heart, which hastens cancer-associated death. miR-486 is a myogenic microRNA and its reduced expression in skeletal muscle is observed in muscular dystrophy. Muscle-specific transgenic expression of miR-486 using muscle creatine kinase promoter (MCK-miR-486) partially rescues skeletal muscle defects in muscular dystrophy animal models. We had previously demonstrated reduced circulating and skeletal muscle levels of miR-486 in several cancer types and lower miR-486 levels correlated with skeletal muscle defects and functional limitations in mammary tumor models. Therefore, skeletal muscle defects induced by cancer could resemble defects observed in various dystrophies, which could be reversed through skeletal muscle expression of miR-486. We performed functional limitations studies and biochemical analysis of skeletal muscles of MMTV-Neu transgenic mice that mimic HER2+ breast cancer and MMTV-PyMT transgenic mice that mimic luminal subtype B breast cancer and these mice crossed to MCK-miR-486 transgenic mice. miR-486 significantly prevented tumor-induced reduction in muscle contraction force, grip strength, and rotarod performance in MMTV-Neu, but not in MMTV-PyMT mice. In MMTV-Neu model, miR-486 reversed several of the cancer-induced changes in skeletal muscle including loss of p53, phospho-AKT, and phospho-laminin alpha 2 (LAMA2) and gain of phosphorylation of the pre-mRNA processing factor hnRNPA0 and the splicing factor SRSF10. LAMA2 is a part of the dystrophin-associated glycoprotein complex, and its loss-of-function mutation is associated with congenital muscular dystrophy. Thus, similar to muscular dystrophy, miR-486 has the potential to reverse skeletal muscle defects and cancer burden in select cancer types.

2022-05-19 | PXD028554 | Pride

A scalable, clinically severe pig model for Duchenne muscular dystrophy

Project description:Large animal models for Duchenne muscular dystrophy (DMD) are indispensible for preclinical evaluation of novel diagnostic procedures and treatment strategies. To evaluate functional consequences of Duchenne muscular dystrophy (DMD) in skeletal muscle and myocardium, we used a new genetically engineered dystrophin KO pig model displaying hallmarks of human DMD. Heart and skeletal muscle tissue samples of DMD pigs and wild-type (WT) controls at three different ages were analyzed by label-free proteomics.

2021-12-01 | PXD027772 | Pride

Expression and Splicing Analysis of Myotonic Dystrophy and Other Dystrophic Muscle

Project description:The prevailing patho-mechanistic paradigm for myotonic dystrophy (DM) is that the aberrant presence of embryonic isoforms is responsible for many, if not most, aspects of the pleiotropic disease phenotype. In order to identify such aberrantly expressed isoforms in skeletal muscle of DM type 1 (DM1) and type 2 (DM2) patients, we utilized the Affymetrix exon array to characterize the largest collection of DM samples analyzed to date, and included non-DM dystrophic muscle samples (NMD) as disease controls. For the exon array profiling on the Human Exon 1.0 ST array (Affymetrix Santa Clara, CA) we used a panel of 28 skeletal muscle biopsies from DM1 (n=8), DM2 (n=10), Becker muscular dystrophy, BMD, (n=3), Duchenne muscular dystrophy, DMD (n=1), Tibial muscular dystrophy, TMD, (n=2) and normal skeletal muscle (n=4). Normal control RNAs were purchased commercially. .CEL files were generated with a pre-commercial version of the Affymetrix processing software, and the headers might be non-standard. In our lab, users of the Partek software could use them, whereas users of GeneSpring had to modify the header information.

2016-01-05 | E-GEOD-48828 | biostudies-arrayexpress

Proteome analysis of skeletal muscle samples from a porcine model of Duchenne muscular dystrophy

Project description:Duchenne muscular dystrophy (DMD) is caused by genetic deficiency of dystrophin and characterized by massive structural and functional changes of skeletal muscle tissue, leading to terminal muscle failure. In this project, proteomics data from skeletal muscle of a genetically engineered DMD pig model were investigated in order to confirm muscular fibrosis and MSOT signals.

2020-01-09 | PXD016003 | Pride

Systemic deletion of DMD exon 51 rescues clinically severe Duchenne muscular dystrophy in a pig model lacking DMD exon 52

Project description:Duchenne muscular dystrophy (DMD) is a fatal X-linked disease caused by mutations in the dystrophin (DMD) gene, leading to the complete absence of DMD and progressive degeneration of skeletal and heart muscles. Expression of an internally shortened dystrophin in DMD subjects (DMDΔ52) can be achieved by skipping DMD exon 51 to reframe the transcript. To predict the best possible outcome of this therapeutic strategy, we generated transgenic pigs lacking DMD exon 51 and 52, additionally representing a new model for Becker muscular dystrophy (BMD). To inspect the proteome alterations caused by the different dystrophin mutations in an unbiased and comprehensive manner, we performed a label-free liquid chromatography-tandem mass spectrometry analysis (LC-MS/MS) of myocardial and skeletal muscle samples from wild-type (WT), DMDΔ52 and DMDΔ51-52 pigs.

2023-07-11 | PXD039533 | Pride

Single-cell RNA sequencing of healthy and dystrophic murine skeletal muscle

Project description:Fibrosis and fat replacement in the skeletal muscle is a major complication that leads to a loss of mobility in chronic muscle disorders, such as muscular dystrophy. However, our current knowledge on the in vivo properties of adipogenic stem and precursor cells remains unclear, mainly due to the high cell heterogeneity in skeletal muscles. For this purpose, we used single-cell RNA-sequencing to decomplexify interstitial cell populations in healthy and dystrophic skeletal muscles. We identified a CD142 (F3) positive cell subpopulation in mice and humans that is responsible for the inhibition of adipogenesis. Furthermore, we found a completely altered composition of interstitial cells in muscular dystrophy, with a near absence of the CD142-positive cells. The novel discovery of these adipo-regulatory cells in the skeletal muscle aids our understanding regarding the aberrant fat deposition in muscular dystrophy, paving the way for treatments that potentially sustain ambulation in patients with muscular dystrophy.

2020-04-02 | GSE147883 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data