title: The pathogenesis of molybdenum cofactor deficiency, its delay by maternal clearance, and its expression pattern in microarray analysis.
abstract: Molybdenum cofactor (Moco)-deficiency is a lethal autosomal recessive disease, for which until now no effective therapy is available. The biochemical hallmark of this disorder is the inactivity of the Moco-dependent sulfite oxidase, which results in elevated sulfite and diminished sulfate levels throughout the organism. In humans, Moco-deficiency results in neurological damage, which is apparent in untreatable seizures and various brain dysmorphisms. We have recently described a murine model for Moco-deficiency, which reflects all enzyme and metabolite changes observed in the patients, and an efficient therapy using a biosynthetic precursor of Moco has been established in this animal model. We now analyzed these mice in detail and excluded morphological brain damage, while expression analysis with microarrays indicates a massive cell death program. This neuronal damage appears to be triggered by elevated sulfite levels and is ameliorated in affected embryos by maternal clearance.
authors.affiliation: Institut für Humangenetik der Universität Göttingen, Heinrich-Düker-Weg 12, 37073 Göttingen, Germany. jreiss@gwdg.de
authors.forename: Jochen
authors.initials: J
authors.lastname: Reiss
authors.forename: Michael
authors.initials: M
authors.lastname: Bonin
authors.forename: Herbert
authors.initials: H
authors.lastname: Schwegler
authors.forename: Jörn Oliver
authors.initials: JO
authors.lastname: Sass
authors.forename: Enrico
authors.initials: E
authors.lastname: Garattini
authors.forename: Silke
authors.initials: S
authors.lastname: Wagner
authors.forename: Heon-Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Engel
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
authors.forename: Günter
authors.initials: G
authors.lastname: Schwarz
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D019755:Carbon-Carbon Lyases; D016000:Cluster Analysis; D003067:Coenzymes / Q000172:deficiency* / Q000493:pharmacokinetics*; D018076:DNA, Complementary; D004195:Disease Models, Animal; D005838:Genotype; D006801:Humans; D008657:Metabolic Clearance Rate; D008667:Metalloproteins / Q000172:deficiency* / Q000493:pharmacokinetics*; D051379:Mice; D018345:Mice, Knockout; D000090006:Molybdenum Cofactors; D009186:Myelin Sheath / Q000473:pathology; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics; D010641:Phenotype; D011621:Pteridines / Q000493:pharmacokinetics*; D012313:RNA / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D019755:Carbon-Carbon Lyases; D003067:Coenzymes; D018076:DNA, Complementary; D008667:Metalloproteins; D000090006:Molybdenum Cofactors; D009687:Nuclear Proteins; D011621:Pteridines; D012313:RNA; C022261:molybdopterin; C491972:Mocs1 protein, mouse