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Series GSE3530 Query DataSets for GSE3530
Status Public on Nov 01, 2005
Title Distinct Gene Expression Profiles in Adult Mouse Heart Following Targeted MAP Kinase Activation
Organism Mus musculus
Experiment type Expression profiling by array
Summary 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.
Keywords: MAP Kinase induction comparison, time course
Overall design αMHC-floxed-HRas-v12/MKK3bE/MKK7D transgenic mice were bred with αMHC-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 -80˚C prior to protein and RNA analysis.
Contributor(s) Mitchell S, Ota A, Foster W, Zhang B, Fang Z, Patel S, Nelson SF, Horvath S, Wang Y
Citation(s) 16368875
Submission date Oct 28, 2005
Last update date Feb 11, 2019
Contact name Scherise Mitchell
Organization name UCLA
Department Anesthesiology
Lab Dr. Yibin Wang
Street address 650 Charles E Young Dr, BH 569 CHS
City Los Angeles
State/province CA
ZIP/Postal code 90095
Country USA
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (36)
GSM80525 Control male replicate1
GSM80526 control male replicate 2
GSM80527 control male replicate 5
BioProject PRJNA93583

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