Compensation For Chronic Oxidative Stress In ALADIN Null Mice

Abstract

BackgroundMutations in the AAAS gene coding for the nuclear pore complex protein ALADIN lead to the autosomal recessive disorder triple A syndrome. Triple A patients present with a characteristic phenotype including alacrima, achalasia and adrenal insufficiency. Patient fibroblasts show increased levels of oxidative stress and several in vitro studies demonstrated that the nucleoporin ALADIN is involved in the cellular oxidative stress response and in adrenal steroidogenesis. We showed that ALADIN knock-out mice lack a phenotype resembling human triple A syndrome. Thus, we hypothesized that application of chronic oxidative stress by ingestion of paraquat will generate triple A-like phenotype in ALADIN null mice.\n\nResultsWe demonstrate that ALADIN knock-out mice present with an unexpected compensated glutathione metabolism still lacking a phenotype resembling human triple A syndrome after application of chronic oxidative stress. We could not observe increased levels of oxidative stress and alterations in adrenal steroidogenesis in mice depleted for ALADIN.\n\nConclusionsThis study stresses the species-specific role of the nucleoporin ALADIN presenting a novel compensatory mechanism of the cellular glutathione redox response and shedding light on the role of ALADIN in the cell.