Cardiovascular phenotype and temperature control in mice lacking thyroid hormone receptor-beta or both alpha1 and beta.
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-alpha1 and -beta (TR-alpha1/beta). The TR-alpha1/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-Tend time in contrast to the TR-alpha1/beta-deficient mice, which exhibited prolonged P-Q and Q-Tend 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-alpha1/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-alpha1 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.
Johansson
C
C
Department of Physiology and Pharmacology, Karolinska Institute, S-171 77 Stockholm, Sweden. Catarina.Johnansson@fyfa.ki.se
Göthe
S
S
Forrest
D
D
Vennström
B
B
Thorén
P
P
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000388:Air; D000818:Animals; D001831:Body Temperature / Q000502:physiology; D001833:Body Temperature Regulation / Q000502:physiology*; D002320:Cardiovascular Physiological Phenomena; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004562:Electrocardiography; D006339:Heart Rate / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009043:Motor Activity / Q000502:physiology; D010641:Phenotype; D010812:Physical Stimulation; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000172:deficiency* / Q000235:genetics
D000319:Adrenergic beta-Antagonists; D018680:Cholinergic Antagonists; D020033:Protein Isoforms; D011988:Receptors, Thyroid Hormone