RT Journal Article
SR Electronic
T1 <span class="sc">d</span>-Aspartate Regulates Melanocortin Formation and Function: Behavioral Alterations in <span class="sc">d</span>-Aspartate Oxidase-Deficient Mice
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2814
OP 2819
DO 10.1523/JNEUROSCI.5060-05.2006
VO 26
IS 10
A1 Huang, Alex S.
A1 Beigneux, Anne
A1 Weil, Zachary M.
A1 Kim, Paul M.
A1 Molliver, Mark E.
A1 Blackshaw, Seth
A1 Nelson, Randy J.
A1 Young, Stephen G.
A1 Snyder, Solomon H.
YR 2006
UL http://www.jneurosci.org/content/26/10/2814.abstract
AB 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/α-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.