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 function in vitro as a retinol dehydrogenase as well as an ethanol dehydrogenase. 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 expressed in adult liver and extrahepatic tissues, being found preferentially in the epithelial cells which are retinoid target tissues. However, human ADH expression patterns have not been analyzed in early embryonic tissues, which are known to synthesize and respond to retinoic acid such as the neural tube and limb buds. To estimate the embryonic expression pattern for one member of the human ADH family, we have constructed transgenic mouse lines carrying the human ADH3 promoter fused to the lacZ gene. ADH3-lacZ transgene expression was first noted at embryonic day 9.5 and was active in the neural tube extending from the midbrain 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 expression 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 including the floor plate and showed a ventral to dorsal gradient of decreasing expression. These findings indicate that at least one human ADH isozyme may exist in the correct tissues to act as an embryonic retinol dehydrogenase catalyzing the synthesis of retinoic acid.
Zgombić-Knight
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Cancer Research Center, La Jolla Cancer Research Foundation, California 92037.
Satre
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Duester
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D000429:Alcohol Oxidoreductases / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D004622:Embryo, Mammalian / Q000502:physiology; D005314:Embryonic and Fetal Development; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009420:Nervous System / Q000196:embryology* / Q000201:enzymology*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015183:Restriction Mapping; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D011993:Recombinant Fusion Proteins; D000429:Alcohol Oxidoreductases; C022520:retinol dehydrogenase; D001616:beta-Galactosidase