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Thyroid Hormone Receptor ß1 Expression in Developing Mouse Limbs and Face¹

Thyroid Study Unit, Department of Medicine, The University of Chicago, Chicago, Illinois 60637

Address all correspondence and requests for reprints to: Leslie J. DeGroot, M.D., Thyroid Study Unit, Mail Code 3090, Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637.

Thyroid hormone, acting through thyroid hormone receptors (TRs), plays an important role in amphibian metamorphosis and vertebrate development. To identify where and when TRß1 promoter is activated during fetal life, we carried out an in vivo functional study of a 1.3 kilobase (kb) TRß1 gene promoter using transgenic mice that express the ß-galactosidase gene under control of the TRß1 promoter. Transactivation of the gene was determined by blue staining of tissues after incubation with X-gal. High expression of transgene was detected in the limbs and face of the 12.5-day-old fetus (12.5F) and 14.5F, reminiscent of the changes occurring during amphibian metamorphosis, and this disappeared at 17.5F. The expression was confined to the tip of finger bones, between fingers in the limb buds, and was detected in the root of whisker follicles, nose, and around the eyes. Signal was detected in the oral cavity, nasal cavity, lung, and urogenital sinus of 14.5F, and disappeared at 17.5F. Signal was detected in the midbrain and auditory vesicles of 9.5F but was reduced between 12.5F and 17.5F, and there was no expression in the cerebral cortex layer of 0 days old neonates (P0). Expression was detected in the cortex after P5. There was signal in the cerebral cortex, cerebellum, kidney, and liver of adult mice. TRß1 messenger RNA was detected by RT-PCR in the developing limbs and face. Transgene expression in the interdigital tissues, which regress during development, suggests that TRß1 is expressed in mammals in areas undergoing apoptosis as well as in areas undergoing differentiation.

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