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).
|Journal||Biochimica et Biophysica Acta - Proteins and Proteomics|
|Publication status||Published - Sept 2020|
All Science Journal Classification (ASJC) codes
- Analytical Chemistry
- Molecular Biology