TY - JOUR
T1 - Targeted Disruption of the Mouse 3-Phosphoglycerate Dehydrogenase Gene Causes Severe Neurodevelopmental Defects and Results in Embryonic Lethality
AU - Yoshida, Kazuyuki
AU - Furuya, Shigeki
AU - Osuka, Soh
AU - Mitoma, Junya
AU - Shinoda, Yoko
AU - Watanabe, Masahiko
AU - Azuma, Norihiro
AU - Tanaka, Hideyuki
AU - Hashikawa, Tsutomu
AU - Itohara, Shigeyoshi
AU - Hirabayashi, Yoshio
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/1/30
Y1 - 2004/1/30
N2 - 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.
AB - 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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U2 - 10.1074/jbc.C300507200
DO - 10.1074/jbc.C300507200
M3 - Article
C2 - 14645240
AN - SCOPUS:9144270452
VL - 279
SP - 3573
EP - 3577
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 5
ER -