Rat adrenoleukodystrophy-related (ALDR) gene: full-length cDNA sequence and new insight in expression

X-linked adrenoleukodystrophy (X-ALD) is an inherited demyelinating disorde r due to mutations in the ALD gene, which encodes a peroxisomal ABC half-tr ansporter (ALDP). It has been suggested that ALDP assembles with ALDRP (adr enoleukodystrophy-related protein), a close homologous half-transporter, to form a functional heterodimer. For the first time full-length ALDRP cDNA ( 5.5 kb) was cloned, and 5' and 3' RACE analysis revealed that alternative u sage of polyadenylation sites generates the two transcripts of 3.0 and 5.5 kb observed in the rat in Northern blot analysis. Southern blotting and chr omosomal mapping demonstrated one ALDR locus in the rat genome. Characteris ation of the 3' flanking region suggested that an ID sequence might be resp onsible for high expression of the 5.5 kb ALDRP transcript in rat brain. AL DR gene expression was found to be high in the liver of rats before weaning and very low in adult rats; the reverse developmental regulation was obser ved in the brain. Fenofibrate, which is a potent inducer of the ALDR gene i n the liver of adult rats, could not induce the ALDR gene in suckling rats. The exact significance of this result with regard to development of an eff icient pharmacological gene therapy for X-ALD is discussed. (C) 2001 Elsevi er Science B.V. All rights reserved.