title: Rat adrenoleukodystrophy-related (ALDR) gene: full-length cDNA sequence and new insight in expression.
abstract: X-linked adrenoleukodystrophy (X-ALD) is an inherited demyelinating disorder due to mutations in the ALD gene, which encodes a peroxisomal ABC half-transporter (ALDP). It has been suggested that ALDP assembles with ALDRP (adrenoleukodystrophy-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 usage 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 chromosomal mapping demonstrated one ALDR locus in the rat genome. Characterisation of the 3' flanking region suggested that an ID sequence might be responsible for high expression of the 5.5 kb ALDRP transcript in rat brain. ALDR 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 observed in the brain. Fenofibrate, which is a potent inducer of the ALDR gene in 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 efficient pharmacological gene therapy for X-ALD is discussed.
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire, Faculté des Sciences Gabriel, Université de Bourgogne, 6 Bd Gabriel, 21000 Dijon, France.
authors.forename: S
authors.initials: S
authors.lastname: Albet
authors.forename: M
authors.initials: M
authors.lastname: Bentejac
authors.forename: S
authors.initials: S
authors.lastname: Savary
authors.forename: C
authors.initials: C
authors.lastname: Gondcaille
authors.forename: A
authors.initials: A
authors.lastname: Netik
authors.forename: J
authors.initials: J
authors.lastname: Berger
authors.forename: C
authors.initials: C
authors.lastname: Szpirer
authors.forename: N
authors.initials: N
authors.lastname: Troffer-Charlier
authors.forename: M
authors.initials: M
authors.lastname: Bugaut
mesh_terms: D020413:3' Untranslated Regions / Q000737:chemistry; D020121:5' Untranslated Regions / Q000737:chemistry; D000074061:ATP Binding Cassette Transporter, Subfamily D; D018528:ATP-Binding Cassette Transporters; D000326:Adrenoleukodystrophy / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000096:biosynthesis / Q000737:chemistry; D011345:Fenofibrate; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D051379:Mice; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; C431694:ABCD2 protein, human; D000074061:ATP Binding Cassette Transporter, Subfamily D; D018528:ATP-Binding Cassette Transporters; D018076:DNA, Complementary; D011506:Proteins; D011345:Fenofibrate