title: Full length cDNA cloning, promoter sequence, and genomic organization of the human adrenoleukodystrophy related (ALDR) gene functionally redundant to the gene responsible for X-linked adrenoleukodystrophy.
abstract: X-linked adrenoleukodystrophy (X-ALD) is a functional defect of the ALD Protein (ALDP), an ABC half-transporter localized in the peroxisomal membrane. It is characterized by defective, very long chain fatty acid (VLCFA) beta-oxidation, resulting in progressive cerebral demyelination. Since individual mutations in the ALD gene may result in a variety of clinical phenotypes, the existence of modifying genetic factors has been proposed. The adrenoleukodystrophy related protein (ALDRP), a close homolog of ALDP, has been shown to complement the defect of VLCFA oxidation if transfected into X-ALD cells or chemically induced in ALDP-deficient mice. Chemical ALDRP induction holds a potential for a novel therapeutic strategy. We report here the exclusively peroxisomal localization of human ALDRP, the full length cDNA, the transcriptional start, and 2.4 kb of the putative promoter region DNA sequence. The human ALDR gene extends over 33 kb on chromosome 12q12 and consists of 10 exons. The gene structure is highly similar to the ALD gene, indicating a recent divergence from a common ancestor. The putative human promoter sequence contains a novel motif conserved in peroxisomal ABC transporters in the mouse. Our data will enable sequence analysis in X-ALD patients to determine a possible role of ALDRP as a modifier and provide tools for the study of therapeutic ALDRP induction.
mesh_terms: D000074061:ATP Binding Cassette Transporter, Subfamily D; D018528:ATP-Binding Cassette Transporters; D000326:Adrenoleukodystrophy / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002881:Chromosomes, Human, Pair 12; D003001:Cloning, Molecular; D018076:DNA, Complementary; D008040:Genetic Linkage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008830:Microbodies / Q000201:enzymology; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D014960:X Chromosome