TY - JOUR
T1 - 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
AU - Romero, Gabriel E.
AU - Lockridge, Amber D.
AU - Morgans, Catherine W.
AU - Bandyopadhyay, Dipankar
AU - Miller, Robert F.
N1 - Publisher Copyright:
© 2014 American Chemical Society.
PY - 2014/9/17
Y1 - 2014/9/17
N2 - 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).
AB - 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).
KW - Capillary electrophoresis
KW - D-Serine
KW - D-amino acid oxidase
KW - NMDA receptor
KW - Retinal development
KW - Serine racemase
UR - http://www.scopus.com/inward/record.url?scp=84920983362&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84920983362&partnerID=8YFLogxK
U2 - 10.1021/cn5000106
DO - 10.1021/cn5000106
M3 - Article
C2 - 25083578
AN - SCOPUS:84920983362
SN - 1948-7193
VL - 5
SP - 848
EP - 854
JO - ACS Chemical Neuroscience
JF - ACS Chemical Neuroscience
IS - 9
ER -