UNRAVELING OF PHYSIOLOGICAL FUNCTIONS OF RETINOIDS USING A DOMINANT-NEGATIVE RETINOIC ACID RECEPTOR

We have constructed dominant-negative retinoic acid receptors by subst ituting a single amino acid which has been found in a dominant-negativ e thyroid hormone receptor, and have expressed the dominant-negative r etinoic acid receptors in the epidermis, a potential target organ of r etinoic acid. The resultant transgenic mice exhibited dramatic suppres sion of epidermal development, demonstrating the absolute requirement of retionic acid in normal skin development. This novel method, target ed expression of the dominant-negative receptor, is theoretically appl icable to any organ, thus opening the way to defining the physiologica l roles of retionic acid as well as other lipophilic hormones during e mbryogenesis as well as in adults.