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Physiol. Genomics 25: 50-59, 2006. First published December 20, 2005; doi:10.1152/physiolgenomics.00224.2005
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Distinct gene expression profiles in adult mouse heart following targeted MAP kinase activation

¹ Department of Physiology, University of Maryland Baltimore, School of Medicine, Baltimore, Maryland
² Department of Anesthesiology, Division of Molecular Medicine, University of California Los Angeles (UCLA) School of Medicine, Los Angeles, California
³ Department of Human Genetics, University of California Los Angeles (UCLA) School of Medicine, Los Angeles, California
⁴ Department of Biostatistics, UCLA School of Public Health, Los Angeles, California

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. 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, MAP kinase kinase (MKK)3, 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 wk) 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 on 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.

cardiomyopathy; gene regulation; transgenic mice

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