Characterization of the adrenoleukodystrophy-related (ALDR, ABCD2) gene promoter: Inductibility by retinoic acid and forskolin

The adrenoleukodystrophy-related gene (ALDR, ABCD2) is a candidate modifier gene and a potential therapeutic target for X-linked adrenoleukodystrophy (ALD), a severe neurodegenerative disease. The ALDR gene is the closest hom ologue of the ALD gene, which encodes a peroxisomal ABC transporter involve d in the catabolism of very-long-chain fatty acids. Administration of fenof ibrate upregulates ALDR expression in rodent liver. As a step toward unders tanding ALDR transcriptional regulation, the mouse and human 5' regions wer e characterized. The human and mouse genes share a 500-bp conserved region that contains potential Sp1- and AP-2-binding sites but no TATA box. Analys is of the 5'-flanking region of ALDR using a luciferase reporter system rev ealed that 1.3 kb of human or mouse 5'-upstream region has functional promo ter activity. In these transfection experiments, promoter activity of both human and mouse genes could be upregulated by 9-cis-retinoic acid and forsk olin, while no effect of PPAR alpha could be detected. (C) 2000 Academic Pr ess.