Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Myotonic dystrophy type 1 (DM1) leads to altered mRNA expression in heart tissue

ABSTRACT: Myotonic dystrophy type 1 (DM1) is a dominantly inherited disease that affects multiple organ systems. Cardiac dysfunction is the second leading cause of death in DM1. We quantified gene expression in heart tissue from a heart-specific DM1 mouse model (EpA960/MCM) which inducibly expresses human DMPK exon 15 containing 960 CUG expanded repeats and that reproduced Celf1 up regulation. To assess if, in addition to splicing and miRNA defects, CUGexp RNA also perturbed the steady state mRNA levels of genes, we carried out a microarray study on wildtype E14, adult, MCM controls and DM1 mouse hearts. As anticipated we noted a large number of genes to be developmentally regulated in wildtype hearts, however, within 72h of induction of CUGexp RNA there appeared to be a coordinate adult-to-embryonic shift in steady state levels of many genes. We identified transcripts over-expressed or under-expressed in hearts of wildtype adult mice, wildtype embryonic day 14 (E14), and DM1 mice induced to express CUGexp RNA for 72h and 1wk, when compared to MCM controls. Multiple group comparison.

ORGANISM(S): Mus musculus

SUBMITTER: Chad Creighton

PROVIDER: E-GEOD-48991 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The Mef2 transcription network is disrupted in myotonic dystrophy heart tissue, dramatically altering miRNA and mRNA expression.

Kalsotra Auinash A Singh Ravi K RK Gurha Priyatansh P Ward Amanda J AJ Creighton Chad J CJ Cooper Thomas A TA

Cell reports 20140109 2

Cardiac dysfunction is the second leading cause of death in myotonic dystrophy type 1 (DM1), primarily because of arrhythmias and cardiac conduction defects. A screen of more than 500 microRNAs (miRNAs) in a DM1 mouse model identified 54 miRNAs that were differentially expressed in heart. More than 80% exhibited downregulation toward the embryonic expression pattern and showed a DM1-specific response. A total of 20 of 22 miRNAs tested were also significantly downregulated in human DM1 heart tiss ...[more]

PMID: 24412363

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Project description:Three major MAP kinase signaling cascades, ERK, p38 and JNK, play significant roles in the development of cardiac hypertrophy and heart failure in response to external stress and neural/hormonal stimuli. In order to study the specific function of each MAP kinase branch in adult heart, we have generated three transgenic mouse models with cardiac specific and temporally regulated expression of activated mutants of Ras, MKK3 and MKK7, which are selective upstream activators for ERK, p38 and JNK, respectively. Gene expression profiles in transgenic adult hearts were determined using cDNA microarrays at both early (4-7 days) and late (2-4 weeks) time points following transgene induction. From this study, we revealed common changes in gene expression among the three models, particularly involving extracellular matrix remodeling. However, distinct expression patterns characteristic for each pathway were also identified in cell signaling, growth and physiology. In addition, genes with dynamic expression differences between early vs. late stages illustrated primary vs. secondary changes upon MAP kinase activation in adult hearts. These results provide an overview to both short term and long term effects of MAP kinase activation in heart and support some common as well as unique roles for each MAP kinase cascade in the development of heart failure. Experiment Overall Design:MHC-floxed-HRas-v12/MKK3bE/MKK7D transgenic mice were bred with MHC-Mer-Cre-Mer (MCM) mice (from Dr. J. Molkentin, Cincinnati Children's Hospital) to generate double transgenic animals harboring both floxed transgenes and Mer-Cre-Mer transgene. At 12 weeks of age the double transgenic mice and non-transgenic littermate controls were treated via i.p. injection of tamoxifen at a dosage of 20mg/kgBW once a day for 3 consecutive days as reported. The hearts were harvested at an early (4-7 days post first tamoxifen injection) and a late (2-4 weeks) time point. Left ventricles were dissected and rapidly frozen in liquid nitrogen and stored at -80C prior to protein and RNA analysis. Transcription profiling of

Dataset Information

Myotonic dystrophy type 1 (DM1) leads to altered mRNA expression in heart tissue

Publications

The Mef2 transcription network is disrupted in myotonic dystrophy heart tissue, dramatically altering miRNA and mRNA expression.

Similar Datasets

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