D-Amino acid oxidase deficiency is caused by a large deletion in the Dao gene in LEA rats

Yukiko Shimizu, Chiharu Ishii, Rieko Yanobu-Takanashi, Kenta Nakano, Akio Imaike, Masashi Mita, Kenji Hamase, Tadashi Okamura

Research output: Contribution to journalArticle

Abstract

D-Amino acids, enantiomers of L-amino acids, are increasingly recognized as physiologically active molecules as well as potential biomarkers for diseases. D-Amino acid oxidase (DAO) catalyzes the oxidative deamination of D-amino acids and is present in a wide variety of organisms from yeasts to humans. Previous studies indicated that LEA rats lacked DAO activity, and levels of D-Ser and D-Ala were markedly increased in their tissues, suggesting a mutated locus responsible for the lack of Dao activity (ldao) existed in the LEA genome. Sequence analysis identified deletion breakpoints located in intron 4–5 of the Dao gene and intron 1–2 of the Svop gene, resulting in a 54.1-kb deletion which encompassed exons 5–12 of the Dao gene and exons 2–16 of the Svop gene. We developed a novel congenic rat strain, F344-Daoldao, harboring the Daoldao mutation from LEA rats delivered onto the F344 genetic background. Compared to the parental F344 strain, in F344-Daoldao rats D-Ala was markedly increased in both cerebrum and cerebellum, while D-Ser content was increased in cerebellum but not cerebrum. D-Ala, D-Ser, D-Pro and D-Leu levels were also elevated in F344-Daoldao plasma. F344-Daoldao rats represent a novel model system that will aid in elucidating the physiological functions of D-amino acids in vivo. (203 words).

Original languageEnglish
Article number140463
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1868
Issue number9
DOIs
Publication statusPublished - Sep 2020

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology

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