Cardiac tissue-specific repression of CELF activity disrupts alternative splicing and causes cardiomyopathy.

ABSTRACT: Members of the CELF family of RNA binding proteins have been implicated in alternative splicing regulation in developing heart. Transgenic mice that express a nuclear dominant-negative CELF protein specifically in the heart (MHC-CELFDelta) develop cardiac hypertrophy and dilated cardiomyopathy with defects in alternative splicing beginning as early as 3 weeks after birth. MHC-CELFDelta mice exhibit extensive cardiac fibrosis, severe cardiac dysfunction, and premature death. Interestingly, the penetrance of the phenotype is greater in females than in males despite similar levels of dominant-negative expression, suggesting that there is sex-specific modulation of splicing activity. The cardiac defects in MHC-CELFdelta mice are directly attributable to reduced levels of CELF activity, as cros

SUBMITTER: Ladd AN 

PROVIDER: S-EPMC1168813 | biostudies-literature | 2005 Jul

REPOSITORIES: biostudies-literature