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 journalArticlepeer-review

13 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

Bibliographical note

Publisher Copyright:
© 2014 American Chemical Society.

Keywords

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

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