THYROID-HORMONE RECEPTOR GENE KNOCKOUTS

The thyroid hormone receptor genes, TR alpha and TR beta, differ in de velopmental expression and tissue distribution. TR beta knockout mice have goiter, elevated thyroid hormone and TSH levels, and a functional auditory defect. In contrast, mice with TR alpha 1/alpha 2 inactivati on have thyroid hypoplasia, low serum thyroid hormone levels, growth a rrest and delayed small intensive maturation. Mice with selective TR a lpha 1 inactivation have apparent normal growth and development, but h ave bradycardia and reduced body temperature. The dramatic differences between these mice with TR beta and TR alpha gene inactivations indic ate the differential functional of these genes. The influence of these gene inactivations on thyroid-stimulating hormone regulation is centr al to the resulting phenotypes.