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

We have constructed dominant-negative retinoic acid receptors (RARs) by substituting single amino acid which has been found in a dominant-negative thyroid hormone receptor, and have expressed the dominant-negative RAR in the epidermis, a potential target organ of retinoic acid (RA). The resultant transgenic mice exhibited dramatic suppression of epidermal development, demonstrating the absolute requirement of RA in normal skin development. This method is theoretically applicable to every organ, thus opening the way to define the physiological roles of RA during embryogenesis as well as in adults.