Loss of Prox1 in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy.

ABSTRACT: 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 requiremen

SUBMITTER: Petchey LK 

PROVIDER: S-EPMC4084422 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature