Targeted disruption of the mouse 3-phosphoglycerate dehydrogenase gene causes severe neurodevelopmental defects and results in embryonic lethality.
J Biol Chem
; 279(5): 3573-7, 2004 Jan 30.
Article
em En
| MEDLINE
| ID: mdl-14645240
ABSTRACT
D-3-Phosphoglycerate dehydrogenase (Phgdh; EC 1.1.1.95) is the first committed enzyme of L-serine biosynthesis in the phosphorylated pathway. To determine the physiological importance of Phgdh-dependent L-serine biosynthesis in vivo, we generated Phgdh-deficient mice using targeted gene disruption in embryonic stem cells. The absence of Phgdh led to a drastic reduction of L-serine metabolites such as phosphatidyl-L-serine and sphingolipids. Phgdh null embryos have small bodies with abnormalities in selected tissues and died after days post-coitum 13.5. Striking abnormalities were evident in the central nervous system in which the Phgdh null mutation culminated in hypoplasia of the telencephalon, diencephalon, and mesencephalon; in particular, the olfactory bulbs, ganglionic eminence, and cerebellum appeared as indistinct structures. These observations demonstrate that the Phgdh-dependent phosphorylated pathway is essential for normal embryonic development, especially for brain morphogenesis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desidrogenases de Carboidrato
/
Sistema Nervoso
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article