Hoffmann I, Ang H L, Duester G
Gene Regulation Program, Burnham Institute, La Jolla, California 92037, USA.
Dev Dyn. 1998 Nov;213(3):261-70. doi: 10.1002/(SICI)1097-0177(199811)213:3<261::AID-AJA3>3.0.CO;2-V.
Mammalian alcohol dehydrogenases ADH1 (class I ADH) and ADH4 (class IV ADH) function as retinol dehydrogenases contributing to the synthesis of retinoic acid, the active form of vitamin A involved in growth and development. Xenopus laevis ADH1 and ADH4 genes were isolated using polymerase chain reaction primers corresponding to conserved motifs of vertebrate ADHs. The predicted amino acid sequence of Xenopus ADH1 was clearly found to be an ortholog of ADH1 from the related amphibian Rana perezi. Phylogenetic tree analysis of the Xenopus ADH4 sequence suggested this enzyme is likely to be an ADH4 ortholog, and this classification was more confidently made when based also on the unique expression patterns of Xenopus ADH1 and ADH4 in several retinoid-responsive epithelial tissues. Northern blot analysis of Xenopus adult tissues indicated nonoverlapping patterns of ADH expression, with ADH1 mRNA found in small intestine, large intestine, liver, and mesonephros and ADH4 mRNA found in esophagus, stomach, and skin. These nonoverlapping tissue-specific patterns are identical to those previously observed for mouse ADH1 and ADH4, thus providing further evidence that Xenopus ADH1 and ADH4 are orthologs of mouse ADH1 and ADH4, respectively. During Xenopus embryonic development ADH1 mRNA was first detectable by Northern blot analysis at stage 35, whereas ADH4 mRNA was undetectable through stage 47. Whole-mount in situ hybridization indicated that ADH1 expression was first localized in the pronephros during Xenopus embryogenesis, thus conserved with mouse embryonic ADH1 which is first expressed in the mesonephros. ADH4 expression was not detected in Xenopus embryos by whole-mount in situ hybridization but was localized to the gastric mucosa of the adult stomach, a property shared by mouse ADH4. Conserved expression of ADH1 and ADH4 in retinoid-responsive epithelial tissues of amphibians and mammals argue that these enzymes may perform essential retinoid signaling functions during development of the pronephros, mesonephros, liver, and lower digestive tract in the case of ADH1 and in the skin and upper digestive tract in the case of ADH4.
哺乳动物酒精脱氢酶ADH1（I类ADH）和ADH4（IV类ADH）作为视黄醇脱氢酶发挥作用，有助于视黄酸的合成，视黄酸是参与生长和发育的维生素A的活性形式。使用对应于脊椎动物ADH保守基序的聚合酶链反应引物分离非洲爪蟾ADH1和ADH4基因。明显发现非洲爪蟾ADH1的预测氨基酸序列是相关两栖动物泽陆蛙ADH1的直系同源物。对非洲爪蟾ADH4序列的系统发育树分析表明，这种酶可能是ADH4的直系同源物，并且当也基于非洲爪蟾ADH1和ADH4在几种类视黄醇反应性上皮组织中的独特表达模式时，这种分类更具可信度。对非洲爪蟾成年组织的Northern印迹分析表明ADH表达模式不重叠，在小肠、大肠、肝脏和中肾中发现ADH1 mRNA，在食管、胃和皮肤中发现ADH4 mRNA。这些不重叠的组织特异性模式与先前在小鼠ADH1和ADH4中观察到的模式相同，从而进一步证明非洲爪蟾ADH1和ADH4分别是小鼠ADH1和ADH4的直系同源物。在非洲爪蟾胚胎发育过程中，通过Northern印迹分析在第35阶段首次可检测到ADH1 mRNA，而在第47阶段之前未检测到ADH4 mRNA。整体原位杂交表明，在非洲爪蟾胚胎发生过程中，ADH1表达首先定位于前肾，因此与首先在中肾中表达的小鼠胚胎ADH1一致。通过整体原位杂交在非洲爪蟾胚胎中未检测到ADH4表达，但在成年胃的胃黏膜中定位，这是小鼠ADH4共有的特性。ADH1和ADH4在两栖动物和哺乳动物的类视黄醇反应性上皮组织中的保守表达表明，这些酶可能在ADH1的情况下在前肾、中肾、肝脏和下消化道发育过程中以及在ADH4的情况下在皮肤和上消化道发育过程中执行重要的类视黄醇信号传导功能。
