The pathogenesis of molybdenum cofactor deficiency, its delay by maternal clearance, and its expression pattern in microarray analysis

Jochen Reiss, Michael Bonin, Herbert Schwegler, Jörn Oliver Sass, Enrico Garattini, Silke Wagner, Heon Jin Lee, Wolfgang Engel, Olaf Riess, Günter Schwarz

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)12-20
Number of pages9
JournalMolecular Genetics and Metabolism
Volume85
Issue number1
DOIs
Publication statusPublished - May 2005

Keywords

  • Cofactor
  • Maternal clearance
  • MOCS1
  • Molybdenum
  • Sulfite

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Endocrinology, Diabetes and Metabolism

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