The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Targeted Disruption of the Mouse 3-Phosphoglycerate Dehydrogenase Gene Causes Severe Neurodevelopmental Defects and Results in Embryonic Lethality
Open accessAbstract
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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“However, inhibitors of PHGDH might have a limited therapeutic index, as de novo serine synthesis has an important physiological role in the central nervous system (Furuya, 2008) and PHGDH-deficient mice exhibit severe brain morphogenesis defects (Yoshida et al., 2004).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Yoshida et al., 2004
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Cites
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Self-citationThe bHLH Gene Hes1 as a Repressor of the Neuronal Commitment of CNS Stem Cells
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Self-citationFURTHER STUDIES ON THE PATHWAY OF SERINE FORMATION FROM CARBOHYDRATE
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One-Carbon Metabolism in Health and Disease
Ducker, G. S., & Rabinowitz, J. D. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.009 · Cited by 2,239
“Knockout of the serine biosynthetic enzyme phosphoglycerate dehydrogenase (PHGDH) in mice causes severe neurological abnormalities including absence of the olfactory bulb, ganglionic eminence, and cerebellum (Yoshida et al., 2004).”
BackgroundTargeting Metabolism for Cancer Therapy
Luengo, A., Gui, D. Y., & Vander Heiden, M. G. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.08.028 · Cited by 971
“However, inhibitors of PHGDH might have a limited therapeutic index, as de novo serine synthesis has an important physiological role in the central nervous system (Furuya, 2008) and PHGDHdeficient mice exhibit severe brain morphogenesis defects (Yoshida et al., 2004).”
BackgroundSerine and one-carbon metabolism in cancer
Yang, M., & Vousden, K. H. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.81 · Cited by 992
The importance of serine metabolism in cancer
Mattaini, K. R., Sullivan, M. R., & Heiden, M. G. V. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201604085 · Cited by 423
“A genetically engineered mouse with deletion of the PHG DH gene, which encodes the first enzyme of the SSP, shows reduced serine levels in brain (Yoshida et al., 2004), and human patients with mutations in SSP genes show decreased blood serine levels (van der Crabben et al., 2013), suggesting that…”
BackgroundTajan, M., Hennequart, M., Cheung, E. C., Zani, F., Hock, A. K., Legrave, N. M., Maddocks, O. D. K., Ridgway, R. A., Athineos, D., Suárez‐Bonnet, A., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20223-y · Cited by 312
Metadata
- Authors
- Yoshida, K., Furuya, S., Osuka, S., Mitoma, J., Shinoda, Y., Watanabe, M., Azuma, N., Tanaka, H., Hashikawa, T., Itohara, S., & Hirabayashi, Y.
- Affiliations
- RIKEN (JP)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Hokkaido University (JP)
- Utsunomiya University (JP)
- Corresponding author
- Furuya, Shigeki
- Hirabayashi, Yoshio
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-01
- Volume
- 279
- Issue
- 5
- Pages
- 3573-3577
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2097895708
- Cited by
- 161
- References
- 25
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 10 · 2023: 9 · 2022: 7 · 2021: 13 · 2020: 15 · 2019: 4 · 2018: 11 · 2017: 4 · 2016: 8 · 2015: 6 · 2014: 4 · 2013: 3 · 2012: 8
- FWCI
- 2.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- 3-phosphoglycerate dehydrogenase, PHGDH, L-serine biosynthesis, embryonic lethality, neurodevelopmental defects, brain morphogenesis, sphingolipids, olfactory bulb hypoplasia, ganglionic eminence, cerebellum, telencephalon, diencephalon, midbrain
- MeSH terms
- Alleles, Animals, Brain, Carbohydrate Dehydrogenases, Cytosol, Exons, Heterozygote, Immunohistochemistry, Introns, Liver, Mice, Inbred C57BL, Mice, Transgenic, Microscopy, Fluorescence, Mutation, Nervous System, Phenotype, Phosphorylation, Serine, Stem Cells, Time Factors, Blotting, Southern, Blotting, Western, Polymerase Chain Reaction, Phosphoglycerate Dehydrogenase, Mice
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