Nature Communications (Apr 2021)

The Pah-R261Q mouse reveals oxidative stress associated with amyloid-like hepatic aggregation of mutant phenylalanine hydroxylase

  • Oscar Aubi,
  • Karina S. Prestegård,
  • Kunwar Jung-KC,
  • Tie-Jun Sten Shi,
  • Ming Ying,
  • Ann Kari Grindheim,
  • Tanja Scherer,
  • Arve Ulvik,
  • Adrian McCann,
  • Endy Spriet,
  • Beat Thöny,
  • Aurora Martinez

DOI
https://doi.org/10.1038/s41467-021-22107-1
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 16

Abstract

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Phenylketonuria (PKU) is caused by autosomal recessive variants in phenylalanine hydroxylase (PAH) and can lead to neurotoxicity. Here the authors describe a mouse model of PKU based on a mutation in phenylalanine hydroxylase (R261Q) which replicates traits of this disease and shows a proteostasis defect and oxidative stress, implying a gain-of-function contribution to the disease phenotype.