期刊
JOURNAL OF NEUROSCIENCE
卷 26, 期 10, 页码 2814-2819出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.5060-05.2006
关键词
amino acid; neuroendocrine; knock-out mice; aspartate; turnover; behavior; proopiomelanocortin (POMC)
资金
- NCI NIH HHS [CA099506] Funding Source: Medline
- NIAID NIH HHS [AI054384] Funding Source: Medline
- NIAMS NIH HHS [AR050200] Funding Source: Medline
- NIDA NIH HHS [DA00074, DA00266] Funding Source: Medline
- NIMH NIH HHS [MH57535, MH66144] Funding Source: Medline
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.
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