CLONING OF THE MOUSE CLASS-IV ALCOHOL-DEHYDROGENASE (RETINOL DEHYDROGENASE) CDNA AND TISSUE-SPECIFIC EXPRESSION PATTERNS OF THE MURINE ADH GENE FAMILY

Humans possess five classes of alcohol dehydrogenase (ADH), including forms able to oxidize ethanol or formaldehyde as part of a defense mec hanism, as well as forms acting as retinol dehydrogenases in the synth esis of the regulatory ligand retinoic acid. However, the mouse has pr eviously been shown to possess only three forms of ADH. Hybridization analysis of mouse genomic DNA using cDNA probes specific for each of t he five classes of human ADH has now indicated that mouse DNA cross-hy bridizes to only classes I, III, and IV. With human class II or class V ADH cDNA probes, hybridization to mouse genomic DNA was very weak or undetectable, suggesting either a lack of these genes in the mouse or a high degree of mutational divergence relative to the human genes. c DNAs for murine ADH classes I and III have previously been cloned, and we now report the cloning of a full-length mouse class IV ADH cDNA In Northern blot analyses, mouse class TV ADH mRNA was abundant in the s tomach, eye, skin, and ovary, thus correlating with the expression pat tern for the mouse Adh-3 gene previously determined by enzyme analysis . In situ hybridization studies on mouse stomach indicated that class IV ADH transcripts were abundant in the mucosal epithelium but absent from the muscular layer. Comparison of the expression patterns for all three mouse ADH genes indicated that class III was expressed ubiquito usly, whereas classes I and IV were differentially expressed in an ove rlapping set of tissues that all contain a large component of epitheli al cells. This expression pattern is consistent with the ability of cl asses I and IV to oxidize retinol for the synthesis of retinoic acid k nown to regulate epithelial cell differentiation. The results presente d here indicate that the mouse has a simpler ADH gene family than the human but has conserved class IV ADH previously shown to be a very act ive retinol dehydrogenase in humans.