Mutations 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 have demonstrated that the
nucleoporin ALADIN is involved in both the cellular oxidative stress response and adrenal steroidogenesis. It is known that ALADIN knock-out mice lack a phenotype resembling human
triple A syndrome. The objective of this study was to determine whether the application of chronic oxidative stress by ingestion of
paraquat would generate a triple A-like phenotype in ALADIN null mice. Adult male mice were fed either a
paraquat (0.25 g/kg diet) or control diet for 11 days. After application of chronic oxidative stress, ALADIN knock-out mice presented with an unexpected compensated
glutathione metabolism, but lacked a phenotype resembling human
triple A syndrome. We did not observe increased levels of oxidative stress and alterations in adrenal steroidogenesis in mice depleted for ALADIN. This study stresses the species-specific role of the
nucleoporin ALADIN, which in mice involves a novel compensatory mechanism for regulating the cellular
glutathione redox response.