The pathogenesis of molybdenum cofactor deficiency, its delay by maternal clearance, and its expression pattern in microarray analysis |
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Authors: | Reiss Jochen Bonin Michael Schwegler Herbert Sass Jörn Oliver Garattini Enrico Wagner Silke Lee Heon-Jin Engel Wolfgang Riess Olaf Schwarz Günter |
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Affiliation: | Institut für Humangenetik der Universit?t G?ttingen, Heinrich-Düker-Weg 12, 37073 G?ttingen, Germany. jreiss@gwdg.de |
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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. |
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