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-Dao^ldao, harboring the Dao^ldao mutation from LEA rats delivered onto the F344 genetic background. Compared to the parental F344 strain, in F344-Dao^ldao 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-Dao^ldao plasma. F344-Dao^ldao rats represent a novel model system that will aid in elucidating the physiological functions of d-amino acids in vivo. (203 words).

d-氨基酸，l-氨基酸的对映异构体，越来越被认为是生理活性分子以及疾病的潜在生物标记。d-氨基酸氧化酶（DAO）催化d-氨基酸的氧化脱氨作用，并存在于从酵母到人类的各种生物中。先前的研究表明，LEA大鼠缺乏DAO活性，并且其组织中d -Ser和d -Ala的水平显着增加，表明LEA基因组中存在导致Dao活性缺乏的突变位点（ldao）。序列分析确定了位于Dao基因的4-5号内含子和3d的1-2号内含子中的缺失断点。Svop基因，导致54.1kb的缺失，其中包括Dao基因的外显子5-12和Svop基因的外显子2-16 。我们开发了一种新型的同系大鼠品系F344- Dao ^ldao，其中^包含来自LEA大鼠的Dao ^ldao突变，该突变已传递至F344遗传背景。与亲本F344品系相比，在F344- Dao ^ldao大鼠中，小脑和小脑中d- ^Ala均显着增加，而小脑中d -Ser含量增加，而小脑中。d -Ala，d -Ser，d -Pro和d-Leu水平也升高F344-道^LDAO等离子体。F344-刀^岛鼠代表了一种新型的模型系统，该系统将有助于阐明体内d-氨基酸的生理功能。（203个字）。