RNA extracted from the left ventricle of 3 different mouse heart disease models, wild type, mdx, and mdx sln+/- hearts
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE144596 | GEO | 2020/11/24
REPOSITORIES: GEO
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Project description:RNA extracted from the left ventricle of 3 different mouse heart disease models, wild type, mdx, and mdx sln+/- hearts
| PRJNA604175 | ENA
Project description:Duchenne muscular dystrophy (DMD) is an X-linked recessive disease caused by deleterious mutations in the DMD gene, rendering non-functional forms or complete absence of the protein dystrophin. Eccentric contraction-induced force loss is the most robust and reproducible phenotype of dystrophin-deficient skeletal muscle, yet the molecular mechanisms underlying force loss remain obscure. To this end, we utilized the mdx mouse model of DMD, which displays extreme sensitivity to eccentric contractions. An existing mouse line from our lab that overexpresses cytoplasmic gamma-actin specifically in skeletal muscle (mdx/Actg1-TG) was shown to significantly protect mdx muscle against contraction-induced force loss. To understand the mechanism behind this protection, we performed iTRAQ proteomics on mdx/Actg1-TG tibialis anterior (TA) muscle versus non-transgenic littermate controls to identify differentially-expressed proteins that may afford protection upon gamma-actin overexpression.
2018-10-22 | PXD009680 | Pride
Project description:The mdx mouse (C57BL/10ScSn-DMDmdx/J), like Duchenne muscular dystrophy (DMD) patients, lacks the protein dystrophin. However, the mdx mouse has a normal lifespan and mild pathology while DMD remains a severe, fatal disease. New mouse models have been developed that are more severely affected but they have not replaced the mdx mouse in DMD research. A few years ago RNA-sequencing (RNA-seq) results of biopsies from DMD and normal human muscle were published but we could not find equivalent data for the mouse. We now report RNA-sequencing of three wild-type and mdx mouse muscles: the flexor digitorum brevis (FDB), the extensor digitorum longus (EDL), and the soleus (SOL). The FDB, a plantar foot muscle is often used for in vivo and ex vivo experiments but may be less affected by the lack of dystrophy than the hindlimb muscles. We compared muscles from 2- and 5-month old mice to investigate the time-course of the mdx pathology. The results show a muscle- and age-dependent parallel between mdx and DMD muscles. Although the FDB is less affected than EDL and SOL at 2 months, the three muscles show, at both ages, activation of close to 100 genes from 7 pathways that are affected in presymptomatic DMD patients and have been called "DMD disease signature".
2021-06-22 | GSE162455 | GEO
Project description:Analysis of skeletal muscles with specific knockout (KO) of Phosphatase and tensin homolog (Pten) gene in an animal model of DMD (mdx mice). Pten knockout alleviates myofiber degeneration and restores muscle function in mdx mice.
2020-10-06 | GSE150220 | GEO
Project description:Duchenne muscular dystrophy (DMD) is characterized by impaired cytoskeleton organization, cytosolic calcium handling oxidative stress and mitochondrial dysfunction. This results in progressive and fatal muscle damage, wasting and weakness. The Striated Muscle activator of Rho signalling (STARS) is an actin binding protein that activates the myocardin-related transcription factor-A (MRTFA)/serum response factor (SRF) transcriptional pathway; a pathway that regulates cytoskeletal structure, muscle function, growth and repair. Here we investigated the regulation of several members of the STARS signalling pathway in muscle from patients with DMD and the dystrophin-deficient mdx and dko (utrophin‐ and dystrophin‐null) mice. A reduction in protein levels of STARS, SRF and RHOA, and an increase in MRTFA were observed in quadriceps muscle of patients with DMD. STARS, SRF and MRTFA mRNA levels were also decreased in DMD muscle, while Stars mRNA levels were decreased in mdx tibialis anterior (TA) muscle and Srf and Mrtfa mRNAs were decreased in dko TA muscle. Overexpressing the human STARS (hSTARS) protein in mdx TA muscle increased maximal isometric specific force by 13%. This was not associated with changes in muscle mass, fibre cross-sectional area (CSA), fibre type, centralized nuclei or collagen deposition. Proteomics screening identified 31 upregulated and 22 downregulated proteins or individual peptides that were significantly regulated by hSTARS overexpression. Pathway enrichment analysis indicated that hSTARS overexpression regulated the keratin, NRF2 and oxidative phosphorylation (OXPHOS) pathways. These pathways are impaired in dystrophic muscle and regulate cytoskeleton organization, oxidative stress and mitochondrial energy production; processes that are vital for muscle function. We conclude that increasing the STARS protein in dystrophic muscle improves muscle force production, potentially via its regulation of multiple pathways that positively influence cytoskeletal structure, oxidative stress and energy production.
2021-08-12 | PXD024631 | Pride
Project description:Matrix metalloprotease (MMP) -2 has been reported to be up-regulated in skeletal muscle in the lethal X-linked muscle disorder Duchenne muscular dystrophy (DMD), which is caused by loss of dystrophin. However, the role of MMP-2 in dystrophin-deficient muscle is not well known. The aim of this study was to verify the role of MMP-2 in dystrophin-deficient muscle by using mdx mice with genetic ablation of MMP-2 (mdx/MMP-2-/-). Gene expression profiles were analyzed in the skeletal muscle of mdx and mdx/MMP-2-/- mice at 1 and 3 months of age.
2011-02-19 | GSE27129 | GEO
Project description:Duchenne muscular dystrophy (DMD) is an incurable neuromuscular degenerative disease, caused by a mutation in the dystrophin gene. Mdx mice recapitulate DMD features. Here we show that injection of wild-type (WT) embryonic stem cells (ESCs) into mdx blastocysts produces mice with improved pathology. A small fraction of WT ESCs incorporates into the mdx mouse nonuniformly to upregulate protein levels of dystrophin in the skeletal muscle. The chimeric muscle shows reduced regeneration and restores dystrobrevin, a dystrophin-related protein, in areas with high and with low dystrophin content. WT ESC injection also normalizes the amount of fat, a tissue that does not express dystrophin. ESC injection without dystrophin does not prevent the appearance of phenotypes in the skeletal muscle or in the fat. Thus, dystrophin supplied by the ESCs reverses disease in mdx mice globally.
2008-08-30 | GSE12580 | GEO
Project description:We constructed the trans/mdx mice as a novel DMD disease model by crossing transgenic mice and mdx mice. The transgenic and trans/mdx mice have UAA incorporation system that can readthrough the nonsense mutation in the dmd gene with additional UAA. The whole transcriptomics of heart and muscle tissues of 5 mouse groups (n=2) were used to determine whether the introduced UAA incorporation system affect the normal gene expression of mice, or the safety of the system. Groups include: a) wild-type C57BL/6N mice; b) transgenic mice; c) mdx mice; d) trans/mdx mice without UAA; e) trans/mdx mice with UAA (50 mg NAEK every 2-3 day, treated for 4 weeks). The total numbers of expressed genes were around 11,000 in all 5 mouse groups. The expression levels of major genes (logFPKM>0) in 5 mouse groups were also close to each other. These data indicated that the UAA incorporation system was safe and could serve as a potential therapeutic strategy for DMD disease. The transgenic mice with UAA incorporation system we constructed could also cross with other nonsense mutation mice to build more functional animal models.
2020-10-03 | GSE158961 | GEO
Project description:Matrix metalloprotease (MMP) -2 has been reported to be up-regulated in skeletal muscle in the lethal X-linked muscle disorder Duchenne muscular dystrophy (DMD), which is caused by loss of dystrophin. However, the role of MMP-2 in dystrophin-deficient muscle is not well known. The aim of this study was to verify the role of MMP-2 in dystrophin-deficient muscle by using mdx mice with genetic ablation of MMP-2 (mdx/MMP-2-/-). Gene expression profiles were analyzed in the skeletal muscle of mdx and mdx/MMP-2-/- mice at 1 and 3 months of age. Tibialis anterior muscle was isolated from four groups of mice (mdx and mdx/MMP-2-/- mice at 1 and 3 months of age). Total RNA was purified and prepared for hybridization to Affymetrix Mouse Genome 430 2.0 arrays (Affymetrix Inc., Santa Clara, CA, USA) using Affymetrix reagents and protocols. The mRNA levels of differentially expressed genes from gene chip analysis were confirmed by quantitative real-time PCR assay.
2011-02-19 | E-GEOD-27129 | biostudies-arrayexpress
Project description:Duchenne muscular dystrophy (DMD) is an incurable neuromuscular degenerative disease, caused by a mutation in the dystrophin gene. Mdx mice recapitulate DMD features. Here we show that injection of wild-type (WT) embryonic stem cells (ESCs) into mdx blastocysts produces mice with improved pathology. A small fraction of WT ESCs incorporates into the mdx mouse nonuniformly to upregulate protein levels of dystrophin in the skeletal muscle. The chimeric muscle shows reduced regeneration and restores dystrobrevin, a dystrophin-related protein, in areas with high and with low dystrophin content. WT ESC injection also normalizes the amount of fat, a tissue that does not express dystrophin. ESC injection without dystrophin does not prevent the appearance of phenotypes in the skeletal muscle or in the fat. Thus, dystrophin supplied by the ESCs reverses disease in mdx mice globally. Experiment Overall Design: 3-week old mdx (C57BL/10ScSn-Dmdmdx/J, Jax labs) females were superovulated and mated with mdx males (Jax labs). Blastocysts were collected at 3.5 days afer mating, injected with 15 WT or mdx R26 ES cells. Injected blastocysts were then transferred into the uteri of pseudopregnant females and allowed to develop to term. Skeletal muscle from 4 month old chimeric male mice was collected, RNA was isolated and microarray analysis were performed.
2008-10-25 | E-GEOD-12580 | biostudies-arrayexpress