The postnatal development of D-serine in the retinas of two mouse strains, including a mutant mouse with a deficiency in D-amino acid oxidase and a serine racemase knockout mouse

Gabriel E. Romero, Amber D. Lockridge, Catherine W. Morgans, Dipankar Bandyopadhyay, Robert F. Miller

    Research output: Contribution to journalArticle

    12 Scopus citations

    Abstract

    D-Serine, an N-methyl D-aspartate receptor coagonist, and its regulatory enzymes, D-amino acid oxidase (DAO; degradation) and serine racemase (SR; synthesis), have been implicated in crucial roles of the developing central nervous system, yet the functional position that they play in regulating the availability of D-serine throughout development of the mammalian retina is not well-known. Using capillary electrophoresis and a sensitive method of enantiomeric amino acid separation, we were able to determine total levels of D-serine at specific ages during postnatal development of the mouse retina in two different strains of mice, one of which contained a loss-of-function point mutation for DAO while the other was a SR knockout line. Each mouse line was tested against conspecific wild type (WT) mice for each genetic strain. The universal trend in all WT and transgenic mice was a large amount of total retinal D-serine at postnatal age 2 (P2), followed by a dramatic decrease as the mice matured into adulthood (P70-80). SR knockout mice retinas had 41% less D-serine than WT retinas at P2, and 10 times less as an adult. DAO mutant mice retinas had significantly elevated levels of D-serine when compared to WT retinas at P2 (217%), P4 (223%), P8 (194%), and adulthood (227%). (Graph Presented).

    Original languageEnglish (US)
    Pages (from-to)848-854
    Number of pages7
    JournalACS Chemical Neuroscience
    Volume5
    Issue number9
    DOIs
    StatePublished - Sep 17 2014

    Keywords

    • Capillary electrophoresis
    • D-Serine
    • D-amino acid oxidase
    • NMDA receptor
    • Retinal development
    • Serine racemase

    ASJC Scopus subject areas

    • Biochemistry
    • Physiology
    • Cognitive Neuroscience
    • Cell Biology

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