Mouse microsomal class 3 aldehyde dehydrogenase: AHD3 cDNA sequence, inducibility by dioxin and clofibrate, and genetic mapping

We have cloned and sequenced the mouse AHD3 cDNA, which codes for the Class 3 microsomal aldehyde dehydrogenase (ALDH3m), The cDNA is 2,997 bp in length excluding the poly(A)(+) tail, and has 5' and 3' nontranslated regions of 113 bp and 1,429 bp, respectively, The deduced amino acid sequence consists of 484 amino acids, including the first methionine (M(r) = 53,942), and contains a hydrophobic segment at the carboxyl terminus which is the putative membrane anchor, The mouse AHD3 protein was found to be: 95% similar to the rat microsomal ALDH3m protein, 65% identical to the mouse, rat and human cytosolic ALDH3c protein, and <28% similar to the rat Class 1 and Class 2 ALDH and methylmalonate-semialdehyde dehydrogenase proteins, Southern hybridization analysis of mouse cDNA probed with the full-length AHD3 cDNA revealed that the Ahd3 gene likely spans less than a total of 25 kb, The mouse Ahd3 gene is very tightly linked to the Ahd4 gene on chromosome 11, Mouse AHD3 mRNA levels are increased by dioxin in mouse Hepa1c1c7 hepatoma wild-type (wt) cells but not in the Ah receptor nuclear translocator (ARNT)-defective (c4) mutant line, indicating that the induction process is mediated by the Ah (aromatic hydrocarbon) dioxin-binding receptor, AHD3 mRNA levels are also inducible by clofibrate in both the wt and c4 lines, AHD3 mRNA levels are not elevated in the CYP1A1 metabolism-deficient c37 mutant line or as part of the oxidative stress response found in the untreated 14CoS/14CoS mouse cell line, These data indicate that, although inducible by dioxin, the Ahd3 gene does not qualify as a member of the aromatic hydrocarbon [Ah] gene battery.