Deletion of Mocos induces xanthinuria with obstructive nephropathy and major metabolic disorders in mice
Résumé
Background : Xanthinuria type II is a rare autosomal purine disorder. This recessive defect of purine metabolism remains an underrecognized disorder.
Methods : Mice with targeted disruption of the molybdenum cofactor sulfurase (Mocos) gene were generated to enable an integrated understanding of purine disorders and evaluate pathophysiological functions of this gene found in large number of pathways and known to be associated with autism.
Results : Mocos deficient mice die with 4 weeks of age due to renal failure of distinct obstructive nephropathy with xanthinuria, xanthine deposits, cystic tubular dilatation, Tamm Horsfall (uromodulin) protein deposits, tubular cell necrosis with neutrophils and occasionally hypdronephrosis with urolithiasis. Obstructive nephropathy is associated with moderate interstitial inflammatory and fibrotic responses, anemia, reduced detoxification systems and important alterations of the metabolism of purines, amino acids and phospholipids.Conversely, heterozygous mice expressing reduced MOCOS protein are healthy with no apparent
pathology.
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