title: D-aspartate regulates melanocortin formation and function: behavioral alterations in D-aspartate oxidase-deficient mice.
abstract: D-aspartate, an abundant D-amino acid enriched in neuroendocrine tissues, can be degraded by D-aspartate oxidase (Ddo). To elucidate the function of D-aspartate, we generated mice with targeted deletion of Ddo (Ddo(-/-)) and observe massive but selective augmentations of D-aspartate in various tissues. The pituitary intermediate lobe, normally devoid of D-aspartate from endogenous Ddo expression, manifests pronounced increases of immunoreactive D-aspartate in Ddo(-/-) mice. Ddo(-/-) mice show markedly diminished synthesis and levels of pituitary proopiomelanocortin/alpha-MSH, associated with decreased melanocortin-dependent behaviors. Therefore, Ddo is the endogenous enzyme that degrades D-aspartate, and Ddo-enriched organs, low in D-aspartate, may represent areas of high turnover where D-aspartate may be physiologically important.
authors.affiliation: Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Alex S
authors.initials: AS
authors.lastname: Huang
authors.forename: Anne
authors.initials: A
authors.lastname: Beigneux
authors.forename: Zachary M
authors.initials: ZM
authors.lastname: Weil
authors.forename: Paul M
authors.initials: PM
authors.lastname: Kim
authors.forename: Mark E
authors.initials: ME
authors.lastname: Molliver
authors.forename: Seth
authors.initials: S
authors.lastname: Blackshaw
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Nelson
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Young
authors.forename: Solomon H
authors.initials: SH
authors.lastname: Snyder
mesh_terms: D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015152:Blotting, Northern / Q000379:methods; D015992:Body Mass Index; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D050804:D-Aspartate Oxidase / Q000172:deficiency*; D026603:D-Aspartic Acid / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism; D011090:Polyenes / Q000378:metabolism*; D013739:Testosterone / Q000097:blood; D000521:alpha-MSH / Q000378:metabolism
chemical_list: D011090:Polyenes; C436145:melanocrocin; D013739:Testosterone; D010649:Phenylalanine; D026603:D-Aspartic Acid; D000521:alpha-MSH; D050804:D-Aspartate Oxidase