Proceedings of the National Academy of Sciences - PNAS, 2014-07, Vol.111 (26), p.9515-9520
2014
Details
- Autor(en) / Beteiligte
- Titel
- Loss of Prox1 in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2014-07, Vol.111 (26), p.9515-9520
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2014
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Correct regulation of troponin and myosin contractile protein gene isoforms is a critical determinant of cardiac and skeletal striated muscle development and function, with misexpression frequently associated with impaired contractility or disease. Here we reveal a novel requirement for Prospero-related homeobox factor 1 (Prox1) during mouse heart development in the direct transcriptional repression of the fast-twitch skeletal muscle genes troponin T3 , troponin I2 , and myosin light chain 1 . A proportion of cardiac-specific Prox1 knockout mice survive beyond birth with hearts characterized by marked overexpression of fast-twitch genes and postnatal development of a fatal dilated cardiomyopathy. Through conditional knockout of Prox1 from skeletal muscle, we demonstrate a conserved requirement for Prox1 in the repression of troponin T3 , troponin I2 , and myosin light chain 1 between cardiac and slow-twitch skeletal muscle and establish Prox1 ablation as sufficient to cause a switch from a slow- to fast-twitch muscle phenotype. Our study identifies conserved roles for Prox1 between cardiac and skeletal muscle, specifically implicated in slow-twitch fiber-type specification, function, and cardiomyopathic disease.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.1406191111Titel-ID: cdi_crossref_primary_10_1073_pnas_1406191111
- Format
- –
- Schlagworte
- Animals, Biological Sciences, Cardiomyopathy, Dilated - metabolism, Cell Differentiation - physiology, Chromatin Immunoprecipitation, Dilated cardiomyopathy, DNA Primers - genetics, Fast twitch muscle fibers, Fluorescent Antibody Technique, Gene expression, Gene expression regulation, Gene Expression Regulation, Developmental - physiology, Genes, Heart, Homeodomain Proteins - genetics, Mice, Mice, Knockout, Microarray Analysis, Muscle, Striated - embryology, Muscle, Striated - metabolism, Muscles, Muscular system, Myocardium, Myocardium - metabolism, Myosin Light Chains - metabolism, Real-Time Polymerase Chain Reaction, Skeletal muscle, Skeletal system, Slow twitch muscle fibers, Troponin - metabolism, Troponin I - metabolism, Tumor Suppressor Proteins - deficiency, Tumor Suppressor Proteins - genetics