The effect of preproenkephalin gene deletion on heart function in mice

Enkephalins, the endogenous ligands of the µ- and δ-opioid receptors, are abundantly expressed in the nervous system and peripheral organs, including the heart. Accumulating evidence suggests that they participate in cardiac development and act as autocrine and paracrine modulators of heart activity. Here, we investigate the role of enkephalins in cardiac physiology using a newly generated mouse strain with a complete ablation of the preproenkephalin ( Penk ) gene. We find that, although adult mutant mice weighed less, the mutation caused no apparent changes in behavioral phenotype, no increase in anxiety-like behaviors, and only a mild reduction in locomotor activity. There was no effect of Penk deletion on heart weight or size. A comprehensive analysis of left ventricular function using MRI revealed normal basal cardiac performance, except for a significant reduction in the peak fill and ejection rates. There were no significant effects of Penk deletion on left ventricular function after β 1 -adrenergic stimulation with dobutamine. At the same time, we observed the expected significant differences in heart size and function between male and female mice. In conclusion, our data show that enkephalins are not essential for normal heart development and have a moderate impact on adult heart function under basal conditions.