Cardiovascular phenotype and temperature control in mice lacking thyroid hormone receptor-beta or both alpha 1 and beta

Departments of 1 Physiology and Pharmacology and 2 Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden; and 3 Department of Human Genetics, Mount Sinai University, New York, New York 10029 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)- or TR- 1 and - (TR- 1 / ). The TR- 1 / -deficient mice had a reduced heart rate compared with wild-type controls. The TR- -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- -deficient mice had a shortened Q-T end time in contrast to the TR- 1 / -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 -adrenergic-receptor blocker resulted in a parallel decrease in all mice. The TR- 1 / -deficient mice also had a 0.4°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- 1 has a major role in determining heart rate under baseline conditions and body temperature and that TR- mediates a hormone-induced increase in heart rate. knockout mice; heart rate; electrocardiogram