Loss of dihydrolipoyl succinyltransferase (DLST) leads to reduced resting heart rate in the zebrafish.

ABSTRACT: The genetic underpinnings of heart rate regulation are only poorly understood. In search for genetic regulators of cardiac pacemaker activity, we isolated in a large-scale mutagenesis screen the embryonic lethal, recessive zebrafish mutant schneckentempo (ste). Homozygous ste mutants exhibit a severely reduced resting heart rate with normal atrio-ventricular conduction and contractile function. External electrical pacing reveals that defective excitation generation in cardiac pacemaker cells underlies bradycardia in ste (-/-) mutants. By positional cloning and gene knock-down analysis we find that loss of dihydrolipoyl succinyltransferase (DLST) function causes the ste phenotype. The mitochondrial enzyme DLST is an essential player in the citric acid cycle that warrants proper adenosine-tr

SUBMITTER: Keßler M 

PROVIDER: S-EPMC4335124 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature