Unravelling of physiological functions of retinoids using a dominant-negative retinoic acid receptor.

We have constructed dominant-negative retinoic acid receptors by substituting a single amino acid which has been found in a dominant-negative thyroid hormone receptor, and have expressed the dominant-negative retinoic acid receptors in the epidermis, a potential target organ of retinoic acid. The resultant transgenic mice exhibited dramatic suppression of epidermal development, demonstrating the absolute requirement of retionic acid in normal skin development. This novel method, targeted expression of the dominant-negative receptor, is theoretically applicable to any organ, thus opening the way to defining the physiological roles of retionic acid as well as other lipophilic hormones during embryogenesis as well as in adults.