Cardiovascular phenotype and temperature control in mice lacking thyroid hormone receptor-β or both α1 and β

We have used a telemetry system to record heart rate, body temperature, electrocardiogram (ECG), and locomotor activity in awake, freely moving mice lacking thyroid hormone receptor (TR)-beta or TR-alpha(1) and -beta (TR-alpha(1)/beta). The TR-alpha(1)/beta-deficient mice had a reduced heart rate compared with wild-type controls. The TR-beta-deficient mice showed an elevated heart rate, which, however, was unresponsive to thyroid hormone treatment regardless of hormonal serum levels. ECG revealed that the TR-beta-deficient mice had a shortened Q-T-end time in contrast to the TR-alpha(1)/beta-deficient mice, which exhibited prolonged P-Q and Q-T-end times. Mental or pharmacological stimulation of the sympathetic nervous system resulted in a parallel increase in heart rate in all animals. A single injection of a nonselective beta-adrenergic-receptor blocker resulted in a parallel decrease in all mice. The TR-alpha(1)/beta-deficient mice also had a 0.4 degrees C lower body temperature than controls, whereas no difference was observed in locomotor activity between the different strains of mice. Our present and previous results support the hypothesis that TR-alpha(1) has a major role in determining heart rate under baseline conditions and body temperature and that TR-beta mediates a hormone-induced increase in heart rate.