DIFFERENTIAL ACTIVITY OF THE PROMOTER FOR THE HUMAN ALCOHOL-DEHYDROGENASE (RETINOL DEHYDROGENASE) GENE ADH3 IN NEURAL-TUBE OF TRANSGENIC MOUSE EMBRYOS

Mammalian alcohol dehydrogenase (ADH) has previously been shown to fun ction in vitro as a retinol dehydrogenase as well as an ethanol dehydr ogenase. Thus, ADH participates in the conversion of retinol (vitamin A alcohol) to retinoic acid, a regulatory ligand for the retinoic acid receptor class of transcription factors. Human ADH exists as a family of isozymes encoded by seven genes, which are differentially expresse d in adult liver and extrahepatic tissues, being found preferentially in the epithelial cells which are retinoid target tissues. However, hu man ADH expression patterns have not been analyzed in early embryonic tissues, which are known to synthesize and respond to retinoic acid su ch as the neural tube and limb buds. To estimate the embryonic express ion pattern for one member of the human ADH family, we have constructe d transgenic mouse lines carrying the human ADH3 promoter fused to the lacZ gene. ADH3-lacZ transgene expression was first noted at embryoni c day 9.5 and was active in the neural tube extending from the midbrai n to the spinal cord, as well as the heart and proximal regions of the forelimb buds. In day 12.5 and 13.5 embryos, ADH3 transgene expressio n remained in the neural tube and heart and was also observed in more distal regions of the forelimb and hindlimb buds as well as the kidney . Expression in the neural tube was highest in the ventral midline inc luding the floor plate and showed a ventral to dorsal gradient of decr easing expression. These findings indicate that at least one human ADH isozyme may exist in the correct tissues to act as an embryonic retin ol dehydrogenase catalyzing the synthesis of retinoic acid.