Molecular characterization of the mouse very-long-chain acyl-CoA dehydrogenase gene

Very-long-chain acyl-CoA dehydrogenase (ACADVL, human gene symbol; Acadvl, mouse gene symbol) catalyzes 2,3-dehydrogenation of acyl-CoA thioesters in the mitochondrial long-chain fatty acid beta -oxidation system. This enzyme is a mitochondrial inner membrane-associated protein and a homodimer. It is active toward CoA esters of long-chain and very-long-chain fatty acids. Specific activity of very-long-chain acyl-CoA dehydrogenase with palmitoyl-CoA is higher than that of long-chain acyl-CoA dehydrogenase (Izai et al. 1992). Deficiency of human ACADVL has been identified (Aoyama et al. 1993). Clinical features of this deficiency that are severe include fasting-induced nonketotic hypoglycemia accompanying dicarboxylic aciduria, hepatocellular dysfunction, severe lipid storage in organs, and cardiac disease, in particular hypertrophic cardiomyopathy (Aoyama et al. 1995b). Mitochondrial beta -oxidation enzyme deficiencies often result in sudden death during childhood (Hale and Bennett 1992). cDNA and genomic DNA encoding the human ACADVL were cloned and sequenced (Aoyama et al. 1995a; Orii et al. 1995; Strauss et al. 1995), and several different mutations in the patients were identified (Aoyama et al. 1995a; Souri et al. 1996). For a better understanding of how this enzyme is genetically regulated in vivo and in vitro, use of a model is to be desired. As there has been no information on mouse Acadvl, we isolated and characterized Acadvl cDNA and genomic DNA containing the 5'-flanking region, and determined the chromosomal localization. This is the initial report of the genomic structure of this gene in rodents and the 5'-flanking region in any species (DBO).