MOUSE DIOXIN-INDUCIBLE CYTOSOLIC ALDEHYDE DEHYDROGENASE-3 - AHD4 CDNA SEQUENCE, GENETIC-MAPPING, AND DIFFERENCES IN MESSENGERRNA LEVELS

作者：VASILIOU V; REUTER SF; KOZAK CA; NEBERT DW

来源：Pharmacogenetics, 1993, 3(6): 281-290.

DOI：10.1097/00008571-199312000-00002

We have cloned and sequenced the murine AHD4 cDNA encoding the 'Class 3' cytosolic aldehyde dehydrogenase (ALDH-3c). The cDNA is 1722 bp in length, excluding the poly(A+) tail, and has 5' and 3' nontranslated regions of 174 bp and 186 bp, respectively. AHD4 encodes a protein of 453 amino acids, including the first methionine (M(r) = 50 466). The murine AHD4 protein is 91% and 80% similar to the rat and human ALDH3c proteins, respectively, 64% identical to the rat microsomal ALDH 3 protein, and < 28% similar to ALDH 'Class 1' and 'Class 2' proteins. Surprisingly, in contrast to the rat gene that is expressed in both cell cultures and the intact liver, the murine Ahd-4 gene is inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) or benzo[a]pyrene in cell cultures but not in liver of the intact adult or newborn mouse. Southern hybridization analysis of mouse DNA probed with the full-length cDNA reveals that the Ahd-4 gene is likely to span less than a total of 15 kb, and was mapped to chromosome (Chr) 11 between the Mgat-1 and Shbg loci by analysis of two multilocus crosses. AHD4 mRNA levels are strikingly elevated in the untreated mouse hepatoma Hepa-1c1c7 mutant line c37 lacking CYP1A1 (aryl hydrocarbon hydroxylase) activity and in the untreated 14CoS/14CoS mouse cell line having a homozygous deletion of about 1.2 cM on Chr 7. Our data suggest that the Ahd-4 gene in murine cell cultures is regulated by three distinct mechanisms: Ah receptor-mediated induction by TCDD or benzo[a]pyrene, CYP1A] metabolism-dependent repression, and Chr 7-mediated putative derepression.

• 出版日期1993-12