Molecular cloning, refined chromosomal mapping and structural analysis of the human gene encoding aldehyde oxidase (AOX1), a candidate for the ALS2 gene
Open Access
- 1 June 1997
- journal article
- other
- Published by Taylor & Francis Ltd in Redox Report
- Vol. 3 (3), 135-144
- https://doi.org/10.1080/13510002.1997.11747101
Abstract
Aldehyde oxidase (AOX) is a member of the xanthine oxidase (XO) family of molybdenum hydroxylase, iron-sulfur flavoproteins and is involved in the metabolism of a wide range of native and xenobiotic compounds. The potentially toxic reduced oxygen intermediates (ROI), hydrogen peroxide (H2O2) and superoxide anion (O2.-), are generated when reduced AOX becomes oxidized by molecular oxygen, raising the possibility for involvement of AOX in pathophysiology. Indeed, ROI generation by AOX has been directly implicated in hepatic ethanol toxicity. A cDNA encoding human AOX has been cloned, sequenced, and identified as AOX1. AOX1 was proposed as a candidate for an autosomal recessive form of amyotrophic lateral sclerosis (ALS2) because a YAC carrying AOX1 was mapped to the ALS2 locus and was expressed in microglial cells of the spinal cord. As a source of H2O2, AOX could mediate motor neuron degeneration. To provide a basis for further analysis of AOX1 in pathophysiology, and to examine the relationship of the human AOX1 gene to the gene for human xanthine dehydrogenase (XDH), we have studied the chromosomal locus encoding AOX1 in humans. In the present communication, we have analyzed P1 artificial chromosomes containing AOX1. Our refined chromosomal mapping by FISH locates AOX1 very centromere proximal in the 2q33 region at 2q32.3–2q33.1. We present the first complete structural map of an AOX gene and provide direct evidence that human XDH and AOX1 are related by a gene duplication event. In addition, 1500 bp of upstream DNA containing the putative AOX1 promoter were sequenced and expressed. In contrast to the amino acid coding regions, AOX1 and XDH promoter sequences exhibit marked divergence that reflects the differential activation of these closely related genes. Evidence is presented that AOX may be polygenic in humans as it is in plants, Dipterans, and mice.Keywords
This publication has 34 references indexed in Scilit:
- Purification, cDNA Cloning, and Tissue Distribution of Bovine Liver Aldehyde OxidasePublished by Elsevier BV ,1995
- Transgenic Mice and Knockout Mutants in the Study of Oxidative Stress in Brain InjuryJournal of Neurotrauma, 1995
- Properties of Rabbit Liver Aldehyde Oxidase and the Relationship of the Enzyme to Xanthine Oxidase and DehydrogenaseJBIC Journal of Biological Inorganic Chemistry, 1995
- The human gene for xanthine dehydrogenase (XDH) is localized on chromosome band 2p22Cytogenetic and Genome Research, 1995
- Mapping of the gene for human xanthine dehydrogenase (oxidase) (XDH) to band p23 of chromosome 2Cytogenetic and Genome Research, 1995
- Assignment of Human Xanthine Dehydrogenase Gene to Chromosome 2p22Genomics, 1994
- Retinal oxidase is identical to aldehyde oxidaseFEBS Letters, 1993
- Enzymes depending on the pterin molybdenum cofactor: sequence families, spectroscopic properties of molybdenum and possible cofactor-binding domainsBiochimica et Biophysica Acta (BBA) - Bioenergetics, 1991
- Genetics and development of ocular oxidases in the mouse: evidence for a new locus (Eox‐l) closely linked with the aldehyde oxidase loci on chromosome 1Animal Genetics, 1988
- The oxidation of azaheterocycles with mammalian liver aldehyde oxidaseXenobiotica, 1979