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' non-translated regions of 113 bp and 1,429 bp, respectively. The deduced amino acid sequence consists of 484 amino acids, including the first methionine (Mr = 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 Hepa-1c1c7 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.
Vasiliou
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V
Department of Environmental Health, University of Cincinnati Medical Center, Ohio 45267-0056, USA.
Kozak
C A
CA
Lindahl
R
R
Nebert
D W
DW
D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001483:Base Sequence; D005075:Biological Evolution; D002478:Cells, Cultured; D002994:Clofibrate / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D004147:Dioxins / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008040:Genetic Linkage; D008099:Liver / Q000201:enzymology; D051379:Mice; D008830:Microbodies / Q000187:drug effects; D008861:Microsomes / Q000201:enzymology; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
D000924:Anticholesteremic Agents; D018076:DNA, Complementary; D004147:Dioxins; D012333:RNA, Messenger; D000444:Aldehyde Dehydrogenase; D002994:Clofibrate