Transcriptomics of heart and muscle tissues of transgenic or mdx mice (DMD disease model) with UAA incorporation systems
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ABSTRACT:
PROVIDER: PRJNA667094 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12766224_1.fastq.gz | Fastqsanger.gz | |||
| SRR12766224_2.fastq.gz | Fastqsanger.gz | |||
| SRR12766225_1.fastq.gz | Fastqsanger.gz | |||
| SRR12766225_2.fastq.gz | Fastqsanger.gz | |||
| SRR12766226_1.fastq.gz | Fastqsanger.gz |
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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.
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Project description:Duchenne Muscular Dystrophy (DMD) is a fatal muscle wasting disorder caused by dystrophin deficiency. Previous work suggested that increased expression of the dystrophin-related protein utrophin in the mdx mouse model of DMD can prevent dystrophic pathophysiology. Physiological tests showed that the transgenic mouse muscle functioned in a way similar to normal muscle. More recently, it has become possible to analyse disease pathways using microarrays, a sensitive method to evaluate the efficacy of a therapeutic approach. We thus examined the gene expression profile of mdx mouse muscle compared to normal mouse muscle and compared the data with that obtained from the transgenic line expressing utrophin. The data confirm that the expression of utrophin in the mdx mouse muscle results in a gene expression profile virtually identical to that seen for the normal mouse. This study confirms that a strategy to up-regulate utrophin is likely to be effective in preventing the disease. Experiment Overall Design: Here we have addressed important question of changes in the global gene expression profile of mdx mouse muscle compared to normal mouse muscle and compared the data with that obtained from the transgenic line (fiona) expressing high level of utrophin on mdx background.
2008-06-15 | E-GEOD-7187 | biostudies-arrayexpress
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:Duchenne Muscular Dystrophy (DMD) is a fatal muscle wasting disorder caused by dystrophin deficiency. Previous work suggested that increased expression of the dystrophin-related protein utrophin in the mdx mouse model of DMD can prevent dystrophic pathophysiology. Physiological tests showed that the transgenic mouse muscle functioned in a way similar to normal muscle. More recently, it has become possible to analyse disease pathways using microarrays, a sensitive method to evaluate the efficacy of a therapeutic approach. We thus examined the gene expression profile of mdx mouse muscle compared to normal mouse muscle and compared the data with that obtained from the transgenic line expressing utrophin. The data confirm that the expression of utrophin in the mdx mouse muscle results in a gene expression profile virtually identical to that seen for the normal mouse. This study confirms that a strategy to up-regulate utrophin is likely to be effective in preventing the disease. Keywords: Global gene expression profile
2008-04-23 | GSE7187 | GEO
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".
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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:We report that ablation of one SLN allele positively affects mouse mdx DMD heart failure model mice by several metrics including intracellular calcium handling.
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Project description:Congenital muscular dystrophy type-1A (Lama2-CMD) and Duchenne Muscular dystrophy (DMD) result from deficiencies of laminin-α2 and dystrophin proteins, respectively. Although both proteins strengthen the sarcolemma, they are implicated in clinically distinct phenotypes. We used RNA-deep sequencing (RNA-Seq) of dy2J/dy2J, Lama2-CMD mouse model, skeletal muscle at 8 weeks of age to elucidate disease pathophysiology. This study is the first report of dy2J/dy2J model whole transcriptome profile. RNA-Seq of the mdx mouse model of DMD and WT mouse was carried as well in order to enable a novel comparison of dy2J/dy2J to mdx. A large group of shared differentially expressed genes (DEG) were found in dy2J/dy2J and mdx models (1,834 common DEG, (FDR) < 0.05). Enrichment pathway analysis using Ingenuity Pathway Analysis (IPA) showed enrichment of inflammation, fibrosis, cellular movement, migration and proliferation of cells, apoptosis and necrosis in both mouse models (p-values 3E-10 – 9E-37). Via Canonical pathway analysis; Actin cytoskeleton, Integrin, ILK, NF-kB, Renin-angiotensin, calcium signaling were also enriched and upregulated in both models (FDR<0.05). Interestingly, significant downregulation of Pax7 was detected in dy2J/dy2J compared to upregulation of this key regeneration gene in mdx mice. Pax3 and Mamstr genes were also downregulated in dy2J/dy2J compared to WT mice. These results may explain the distinct disease course and severity in these models. While the mdx model at that stage shows massive regeneration, the dy2J/dy2J shows progressive dystrophic process. Our data deepen our understanding of the molecular pathophysiology and suggest new targets for additional therapies to upregulate regeneration in Lama2-CMD.
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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.
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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