title: 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.
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%).
authors.affiliation: Department of Neuroscience, and ‡Division of Biostatistics, School of Public Health, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Gabriel E
authors.initials: GE
authors.lastname: Romero
authors.forename: Amber D
authors.initials: AD
authors.lastname: Lockridge
authors.forename: Catherine W
authors.initials: CW
authors.lastname: Morgans
authors.forename: Dipankar
authors.initials: D
authors.lastname: Bandyopadhyay
authors.forename: Robert F
authors.initials: RF
authors.lastname: Miller
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D003605:D-Amino-Acid Oxidase / Q000172:deficiency* / Q000235:genetics; D019075:Electrophoresis, Capillary; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018377:Neurotransmitter Agents / Q000378:metabolism; D019998:Racemases and Epimerases / Q000172:deficiency* / Q000235:genetics; D012160:Retina / Q000254:growth & development* / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D000099300:Serine Racemase
chemical_list: D003605:D-Amino-Acid Oxidase; D018377:Neurotransmitter Agents; D019998:Racemases and Epimerases; D012694:Serine; D000099300:Serine Racemase; C485958:Dao1 protein, mouse
keywords: NMDA receptor; capillary electrophoresis; d-Serine; d-amino acid oxidase; retinal development; serine racemase
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