Early sarcomere and metabolic defects in a zebrafish pitx2c cardiac arrhythmia model.

ABSTRACT: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. The major AF susceptibility locus 4q25 establishes long-range interactions with the promoter of PITX2, a transcription factor gene with critical functions during cardiac development. While many AF-linked loci have been identified in genome-wide association studies, mechanistic understanding into how genetic variants, including those at the 4q25 locus, increase vulnerability to AF is mostly lacking. Here, we show that loss of pitx2c in zebrafish leads to adult cardiac phenotypes with substantial similarities to pathologies observed in AF patients, including arrhythmia, atrial conduction defects, sarcomere disassembly, and altered cardiac metabolism. These phenotypes are also observed in a subset of pitx

SUBMITTER: Collins MM 

PROVIDER: S-EPMC6883774 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature