ABNORMAL HEART-RATE AND BODY-TEMPERATURE IN MICE LACKING THYROID-HORMONE RECEPTOR ALPHA-1

Thyroid hormone, acting through several nuclear hormone receptors, pla ys important roles in thermogenesis, lipogenesis and maturation of the neonatal brain, The receptor specificity for mediating these effects is largely unknown, and to determine this we developed mice lacking th e thyroid hormone receptor TR alpha 1, The mice have an average heart rate 20% lower than that of control animals, both under normal conditi ons and after thyroid hormone stimulation, Electrocardiograms show tha t the mice also have prolonged QRS-and QT(end)-durations. The mice hav e a body temperature 0.5 degrees C lower than normal and exhibit a mil d hypothyroidism, whereas their overall behavior and reproduction are normal. The results identify specific and important roles for TR alpha 1 in regulation of tightly controlled physiological functions, such a s cardiac pacemaking, ventricular repolarisation and control of body t emperature.