دورية أكاديمية
Loss of Prox1 in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy
| العنوان: | Loss of Prox1 in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy |
|---|---|
| المؤلفون: | Petchey, Louisa K., Risebro, Catherine A., Vieira, Joaquim M., Roberts, Tom, Bryson, John B., Greensmith, Linda, Lythgoe, Mark F., Riley, Paul R. |
| المصدر: | Petchey , L K , Risebro , C A , Vieira , J M , Roberts , T , Bryson , J B , Greensmith , L , Lythgoe , M F & Riley , P R 2014 , ' Loss of Prox1 in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy ' , Proceedings of the National Academy of Sciences of the United States of America , vol. 111 , no. 26 , pp. 9515-9520 . https://doi.org/10.1073/pnas.1406191111Test , https://doi.org/10.1073/pnas.1406191111Test |
| سنة النشر: | 2014 |
| المجموعة: | King's College, London: Research Portal |
| مصطلحات موضوعية: | Animals, Cardiomyopathy, Dilated/metabolism, Cell Differentiation/physiology, Chromatin Immunoprecipitation, DNA Primers/genetics, Fluorescent Antibody Technique, Gene Expression Regulation, Developmental/physiology, Homeodomain Proteins/genetics, Mice, Knockout, Microarray Analysis, Muscle, Striated/embryology, Myocardium/metabolism, Myosin Light Chains/metabolism, Real-Time Polymerase Chain Reaction, Troponin/metabolism, Troponin I/metabolism, Tumor Suppressor Proteins/deficiency |
| الوصف: | 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 cardiacspecific 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, andmyosin 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1073/pnas.1406191111 |
| الإتاحة: | https://doi.org/10.1073/pnas.1406191111Test https://kclpure.kcl.ac.uk/portal/en/publications/264e26a3-c0d5-4293-955f-a005e5a0a613Test http://www.scopus.com/inward/record.url?scp=84903748882&partnerID=8YFLogxKTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.995E9FF3 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1073/pnas.1406191111 |
|---|