Suppression of Activated FOXO Transcription Factors in the Heart Prolongs Survival in a Mouse Model of Laminopathies.

ABSTRACT: RATIONALE:Mutations in the LMNA gene, encoding nuclear inner membrane protein lamin A/C, cause distinct phenotypes, collectively referred to as laminopathies. Heart failure, conduction defects, and arrhythmias are the common causes of death in laminopathies. OBJECTIVE:The objective of this study was to identify and therapeutically target the responsible mechanism(s) for cardiac phenotype in laminopathies. METHODS AND RESULTS:Whole-heart RNA sequencing was performed before the onset of cardiac dysfunction in the Lmna-/- and matched control mice. Differentially expressed transcripts and their upstream regulators were identified, validated, and targeted by adeno-associated virus serotype 9-short hairpin RNA constructs. A total of 576 transcripts were upregulated and 233 were downregulated in

SUBMITTER: Auguste G 

PROVIDER: S-EPMC5834384 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature