Cited by 166Amino Acid Enzymes and MetabolismNeurogenesis and neuroplasticity mechanismsMetabolism and Genetic Disorders

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 access

Yoshida, Kazuyuki, Furuya, Shigeki, Osuka, Soh, Mitoma, Junya, Shinoda, Yoko, Watanabe, Masahiko, Azuma, Norihiro, Tanaka, Hideyuki, Hashikawa, Tsutomu, Itohara, Shigeyoshi, Hirabayashi, Yoshio·2004·Journal of Biological Chemistry

DOI 10.1074/jbc.c300507200

Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1074/jbc.c300507200

Cites

25 of 25 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Efficient in vivo manipulation of mouse genomic sequences at the zygote stage.
Lakso, M., Pichel, J. G., Gorman, J. R., Sauer, B., Okamoto, Y., Lee, E., Alt, F. W., & Westphal, H. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.12.5860 · Cited by 1,125
Expression of neuron-specific tubulin defines a novel population in the proliferative layers of the developing telencephalon
Menezes, J., & Luskin, M. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-09-05399.1994 · Cited by 475
Glutamate Transporter GLAST Is Expressed in the Radial Glia–Astrocyte Lineage of Developing Mouse Spinal Cord
Shibata, T., Yamada, K., Watanabe, M., Ikenaka, K., Wada, K., Tanaka, K., & Inoue, Y. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-23-09212.1997 · Cited by 407
Self-citation
The bHLH Gene Hes1 as a Repressor of the Neuronal Commitment of CNS Stem Cells
Nakamura, Y., Sakakibara, S.-I., Miyata, T., Ogawa, M., Shimazaki, T., Weiss, S., Kageyama, R., & Okano, H. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-01-00283.2000 · Cited by 316
l-Serine in disease and development
de Koning, T. J., Snell, K., Durán, M., Berger, R., Poll‐The, B. T., & Surtees, R. A. H. (2003) · Biochemical Journal · doi:10.1042/bj20021785 · Cited by 304
Enzymes of serine metabolism in normal, developing and neoplastic rat tissues
Snell, K. (1984) · Advances in Enzyme Regulation · doi:10.1016/0065-2571(84)90021-9 · Cited by 267
3-Phosphoglycerate Dehydrogenase, a Key Enzyme forl-Serine Biosynthesis, Is Preferentially Expressed in the Radial Glia/Astrocyte Lineage and Olfactory Ensheathing Glia in the Mouse Brain
Yamasaki, M., Yamada, K., Furuya, S., Mitoma, J., Hirabayashi, Y., & Watanabe, M. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-19-07691.2001 · Cited by 215
Self-citation
l -Serine and glycine serve as major astroglia-derived trophic factors for cerebellar Purkinje neurons
Furuya, S., Tabata, T., Mitoma, J., Yamada, K., Yamasaki, M., Makino, A., Yamamoto, T., Watanabe, M., Kano, M., & Hirabayashi, Y. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.200364497 · Cited by 197
Self-citation
FURTHER STUDIES ON THE PATHWAY OF SERINE FORMATION FROM CARBOHYDRATE
Ichihara, A., & Greenberg, D. M. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)65032-x · Cited by 187
Cre-mediated germline mosaicism: a method allowing rapid generation of several alleles of a target gene
Holzenberger, M. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.21.e92 · Cited by 129

Show all 25 references

Research works printed but not linked: 1

Bligh, 1959, Can. J. Med. Sci., 37, 911

Sorted by citations

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).”
Background
Targeting 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).”
Background
Serine 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…”
Background
Serine synthesis pathway inhibition cooperates with dietary serine and glycine limitation for cancer therapy
Tajan, 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
Serine in plants: biosynthesis, metabolism, and functions
Ros, R., Muñoz-Bertomeu, J., & Krueger, S. (2014) · Trends in Plant Science · doi:10.1016/j.tplants.2014.06.003 · Cited by 279
L-serine synthesis in the central nervous system: a review on serine deficiency disorders.
Tabatabaie, L., Klomp, L., Berger, R., & de Koning, T. D. (2010) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2009.10.012 · Cited by 185
d-Amino acids in the central nervous system in health and disease
Fuchs, S. A., Berger, R., Klomp, L. W. J., & de Koning, T. J. (2005) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2005.03.003 · Cited by 192
“Of the diVerent pathways involved in Lserine biosynthesis, the glucose-3-phosphoglycerate-3phosphoserine-biosynthesis pathway is essential for normal embryonic development, especially for brain morphogenesis [32].”
Background
Serine Synthesis via PHGDH Is Essential for Heme Production in Endothelial Cells
Vandekeere, S., Dubois, C., Kalucka, J. M., Sullivan, M. R., García‐Caballero, M., Goveia, J., Chen, R., Diehl, F. F., Bar-Lev, L., Souffreau, J., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.06.009 · Cited by 191
Self-citation
Ganglioside Biochemistry
Kolter, T. (2012) · ISRN Biochemistry · doi:10.5402/2012/506160 · Cited by 167
“In agreement with this observation, genetically engineered rodents with deficient phosphoglycerate dehydrogenase required for L-serine formation from D-glucose show drastically reduced ganglioside levels, defects in brain morphogenesis, and drastically reduced lifespan [129, 130].”
Background
A detailed genome-wide reconstruction of mouse metabolism based on human Recon 1
Sigurdsson, M. I., Jamshidi, N., Steingrimsson, E., Thiele, I., & Palsson, B. Ø. (2010) · BMC Systems Biology · doi:10.1186/1752-0509-4-140 · Cited by 154
“The simulation results are therefore consistent with hypertriglyceridemia resulting from LPL mutations, as previously demonstrated with the mouse knockout model [37-51].”
Result
Neu-Laxova Syndrome Is a Heterogeneous Metabolic Disorder Caused by Defects in Enzymes of the L-Serine Biosynthesis Pathway
Acuña‐Hidalgo, R., Schanze, D., Kariminejad, A., Nordgren, A., Kariminejad, M. H., Conner, P., Grigelioniené, G., Nilsson, D., Nordenskjöld, M., Wedell, A., et al. (2014) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2014.07.012 · Cited by 158
“We thus speculate that NLS is still not the ultimate end of the spectrum and that the most severe mutations leading to a complete defect of PSAT or PHGDHmight lead to a phenotype with very early prenatal lethality that has not yet been recognized; this is in line with the finding that mice with homozygous Phgdh knocko…”
Result
Brain-specific Phgdh Deletion Reveals a Pivotal Role for l-Serine Biosynthesis in Controlling the Level of d-Serine, an N-methyl-d-aspartate Receptor Co-agonist, in Adult Brain
Yang, J. H., Wada, A., Yoshida, K., Miyoshi, Y., Sayano, T., Esaki, K., Kinoshita, M. O., Tomonaga, S., Azuma, N., Watanabe, M., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.187443 · Cited by 153
Self-citation
The expression and functions of glycoconjugates in neural stem cells
Yanagisawa, M., & Yu, R. K. (2007) · Glycobiology · doi:10.1093/glycob/cwm018 · Cited by 136
Roles of l-serine and sphingolipid synthesis in brain development and neuronal survival
Hirabayashi, Y., & Furuya, S. (2008) · Progress in Lipid Research · doi:10.1016/j.plipres.2008.01.003 · Cited by 134
“5 Reduced serine and serine-derived lipids [55]”
BackgroundMethodInfluentialSelf-citation
The complexity of the serine glycine one-carbon pathway in cancer
Reina‐Campos, M., Díaz-Meco, M. T., & Moscat, J. (2019) · The Journal of Cell Biology · doi:10.1083/jcb.201907022 · Cited by 125
“Additionally, the potential role of exogenous serine, and the secondary effects of targeting PHGDH, should be carefully considered when assessing the efficacy of these compounds in vivo (de Koning et al., 2004; Sullivan et al., 2019; Vandekeere et al., 2018; Yoshida et al., 2004).”
Background
Phosphoserine Aminotransferase Deficiency: A Novel Disorder of the Serine Biosynthesis Pathway
Hart, C., Race, V., Achouri, Y., Wiame, E., Sharrard, M. J., Olpin, S. E., Watkinson, J., Bonham, J. R., Jaeken, J., Matthijs, G., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/517888 · Cited by 120
“This is not unexpected, given that, in the mouse Phgdh knockout model, complete enzyme deficiency is incompatible with life at the fetal stage.(14) Although the clinical presentation of patient 1 is very similar to that of patients with 3-phosphoglycerate dehydrogenase deficiency, there are some important differences.”
Background
Neu-Laxova Syndrome, an Inborn Error of Serine Metabolism, Is Caused by Mutations in PHGDH
Shaheen, R., Rahbeeni, Z. A., Alhashem, A. M., Faqeih, E., Zhao, Q., Xiong, Y., Almoisheer, A., Al-Qattan, S. M., Almadani, H. A., Alonazi, N. A., et al. (2014) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2014.04.015 · Cited by 118
“Fourth, mice that completely lack themurine ortholog of PHGDH display a universally lethal phenotype that recapitulates key pathogenic features of NLS.22 The embryos do not usually survive beyond 13.5 days postcoitus, are extremely small in size, and have a limb phenotype (where the terminal limb bud is swollen and fa…”
BackgroundInfluential
Serine biosynthesis and transport defects
El‐Hattab, A. W. (2016) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2016.04.010 · Cited by 111
l-Serine links metabolism with neurotransmission
Maugard, M., Vigneron, P.-A., Bolaños, J. P., & Bonvento, G. (2020) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101896 · Cited by 106
Impaired FcεRI-Dependent Gene Expression and Defective Eicosanoid and Cytokine Production as a Consequence of Fyn Deficiency in Mast Cells
Gomez, G., González‐Espinosa, C., Odom, S., Baez, G., Cid, M. E., Ryan, J. J., & Rivera, J. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.11.7602 · Cited by 107
“20) and of D-3-phosphoglycerate dehydrogenase (a key enzyme in Lserine biosynthesis and thus in lipid and sphingolipid biosynthesis (21)), suggested a possible defect in the production of sphingolipids, phospholipids, and possibly eicosanoids by Fyn-deficient mast cells.”
Background
Improving mesophilic anaerobic digestion of food waste by side-stream thermophilic reactor: Activation of methanogenic, key enzymes and metabolism
Li, W., Zhu, L., Wu, B., Liu, Y., Li, J., Xu, L., Huangfu, X., Shi, D., Gu, L., & Chen, C. (2023) · Water Research · doi:10.1016/j.watres.2023.120167 · Cited by 102
l-Serine Deficiency Elicits Intracellular Accumulation of Cytotoxic Deoxysphingolipids and Lipid Body Formation
Esaki, K., Sayano, T., Sonoda, C., Akagi, T., Suzuki, T., Ogawa, T., Okamoto, M., Yoshikawa, T., Hirabayashi, Y., & Furuya, S. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.603860 · Cited by 100
“Our previous analysis of membrane lipids in embryonic tissues of conventional Phgdh KO mice showed that L-Ser deficiency resulting from Phgdh deletion leads to drastic reduction of major SLs such as GD3 (7), prompting us to investigate the consequences of L-Ser deficiency on SL homeostasis in cells and tissues.”
Self-citation
Serine-deficiency syndromes
de Koning, T. D., & Klomp, L. (2004) · Current Opinion in Neurology · doi:10.1097/00019052-200404000-00019 · Cited by 99
L-serine synthesis via the phosphorylated pathway in humans
Murtas, G., Marcone, G. L., Sacchi, S., & Pollegioni, L. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03574-z · Cited by 89
Mutations in SLC1A4, encoding the brain serine transporter, are associated with developmental delay, microcephaly and hypomyelination
Damseh, N. S., Simonin, A., Jalas, C., Picoraro, J. A., Shaag, A., Cho, M. T., Yaacov, B., Neidich, J., Ashhab, M., Juusola, J., et al. (2015) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2015-103104 · Cited by 86
Mouse Genetics Suggests Cell-Context Dependency for Myc-Regulated Metabolic Enzymes during Tumorigenesis
Nilsson, L. M., Plym Forshell, T. Z., Rimpi, S., Kreutzer, C., Pretsch, W., Bornkamm, G. W., & Nilsson, J. A. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002573 · Cited by 85
“Since Phgdh is essential for neurogenesis [30], Phgdh null embryos die at around embryonic day (E) 13.”
Background
D-3-Phosphoglycerate Dehydrogenase
Grant, G. A. (2018) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2018.00110 · Cited by 84
“The phenotype was associated with embryonic lethality and clearly demonstrated the L-serine biosynthetic pathway was critical (Yoshida et al., 2004).”
Background
PHGDH: a novel therapeutic target in cancer
Lee, C. M., Hwang, Y., Kim, M., Park, Y.-C., Kim, H., & Fang, S. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01268-1 · Cited by 88
“This phenomenon was to the effective penetration of the blood ‒ brain barrier by the compound 91 .”
Background
The Phosphorylated Pathway of Serine Biosynthesis Is Essential Both for Male Gametophyte and Embryo Development and for Root Growth in Arabidopsis
Cascales‐Miñana, B., Muñoz‐Bertomeu, J., Flores‐Tornero, M., Anoman, A. D., Pertusa, J., Alaiz, M., Osorio, S., Fernie, A. R., Segura, J., & Ros, R. (2013) · The Plant Cell · doi:10.1105/tpc.113.112359 · Cited by 82
“In mammals, the de novo synthesis of L-Ser is essential in the development and function of the central nervous system (Yoshida et al., 2004).”
Background
Targeting serine-glycine-one-carbon metabolism as a vulnerability in cancers
Sun, W. Y., Liu, R., Gao, X., Lin, Z., Tang, H., Cui, H., & Zhao, E. (2023) · Biomarker Research · doi:10.1186/s40364-023-00487-4 · Cited by 83
“Due to the fact that both glycine and cysteine are products of serine metabolism, the depletion of serine results in lower GSH levels, whereas the activation of the SGOC pathway increases GSH synthesis [51].”
Background
Metabolomic and immune alterations in long COVID patients with chronic fatigue syndrome
Saito, S., Shahbaz, S., Luo, X., Osman, M. S., Redmond, D., Tervaert, J. W. C., Li, L., & Elahi, S. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1341843 · Cited by 84
Hypoxia tolerance in the Norrin-deficient retina and the chronically hypoxic brain studied at single-cell resolution
Heng, J. S., Rattner, A., Stein-O’Brien, G., Winer, B. L., Jones, B. W., Vernon, H. J., Goff, L. A., & Nathans, J. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1821122116 · Cited by 74
“Because complete disruption of de novo serine synthesis in Phgdh mice leads to severe defects in CNS development (70), it would be interesting to determine whether heterozygosity for Phgdh deficiency alters neuronal function or survival in models of MacTel or other CNS diseases.”
Background
Treatment with amino acids in serine deficiency disorders
de Koning, T. J. (2005) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-006-0269-0 · Cited by 73
“Indeed a 3-PGDH knockout mouse showed a phenotype consistent with a drastic reduction in proliferation of neuronal and glial precursor cells (Yoshida et al 2004).”
Background
Sources and Sinks of Serine in Nutrition, Health, and Disease
Handzlik, M. K., & Metallo, C. M. (2023) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-061021-022648 · Cited by 75
“Furthermore, embryonic deletion of PHGDH in mice leads to hypoplasia of the telencephalon, diencephalon, mesencephalon, olfactory bulbs, ganglionic eminence, and cerebellum (121).”
Background
A Phenotypic Small-Molecule Screen Identifies an Orphan Ligand-Receptor Pair that Regulates Neural Stem Cell Differentiation
Saxe, J. P., Wu, H., Kelly, T. K., Phelps, M. E., Sun, Y. E., Kornblum, H. I., & Huang, J. (2007) · Chemistry & Biology · doi:10.1016/j.chembiol.2007.07.016 · Cited by 66
“One possibility is that P-Ser influences the serine biosynthesis pathway, which has been postulated to be important for neurogenesis [15, 16].”
Amino acid synthesis deficiencies
de Koning, T. J. (2017) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-017-0063-1 · Cited by 66
“The 3-PGDH knock out mouse published some years ago verymuch resembles the NLS phenotype and, so far, rescue of the severe developmental defects in mice with L-serine therapy has not been reported (Yoshida et al 2004).”
The serine synthesis pathway drives osteoclast differentiation through epigenetic regulation of NFATc1 expression
Stegen, S., Moermans, K., Stockmans, I., Thienpont, B., & Carmeliet, G. (2024) · Nature Metabolism · doi:10.1038/s42255-023-00948-y · Cited by 65
“Osteoclast-specific deletion of PHGDH was obtained by crossing Phgdh lox/lox mice (in which Phgdh exons 4 and 5 are flanked by LoxP sites 37 ) with lysozyme 2 gene promoter-Cre ( Lyz2 -Cre) transgenic mice 38 (resulting in Lyz2 -Cre + ; Phgdh lox/lox mice, referred to as Phgdh oc − mice).”
Method
Transcriptional regulatory control of mammalian nephron progenitors revealed by multi-factor cistromic analysis and genetic studies
O’Brien, L. L., Guo, Q., Bahrami‐Samani, E., Park, J., Hasso, S. M., Lee, Y.-J., Fang, A., Kim, A. D., Guo, J., Hong, T. M., et al. (2018) · PLoS Genetics · doi:10.1371/journal.pgen.1007181 · Cited by 56
Metabolism of amino acid neurotransmitters: the synaptic disorder underlying inherited metabolic diseases
Kölker, S. (2018) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-018-0201-4 · Cited by 57
D‐serine in the developing human central nervous system
Fuchs, S. A., DORLAND, L., der Velden, M. G. M. D. S., Hendriks, M. M. W. B., Klomp, L. W. J., Berger, R., & de Koning, T. J. (2006) · Annals of Neurology · doi:10.1002/ana.20977 · Cited by 55
Blood triglyceride levels are associated with DNA methylation at the serine metabolism gene PHGDH
Trương, V., Huang, S., Dennis, J. K., Lemire, M., Zwingerman, N., Aïssi, D., Kassam, I., Perret, C., Wells, P., Morange, P., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-09552-z · Cited by 55
Novel mutations in 3-phosphoglycerate dehydrogenase (PHGDH) are distributed throughout the protein and result in altered enzyme kinetics
Tabatabaie, L., de Koning, T. J., Geboers, A. J. J. M., van den Berg, I. E. T., Berger, R., & Klomp, L. W. J. (2009) · Human Mutation · doi:10.1002/humu.20934 · Cited by 54
On the phenotypic spectrum of serine biosynthesis defects
El‐Hattab, A. W., Shaheen, R., Hertecant, J., Galadari, H., Albaqawi, B. S., Nabil, A., & Alkuraya, F. S. (2016) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-016-9921-5 · Cited by 53
3-Phosphoglycerate dehydrogenase: a potential target for cancer treatment
Li, M., Wu, C., Yang, Y., Zheng, M., Yu, S., Wang, J., Chen, L., & Li, H. (2021) · Cellular Oncology · doi:10.1007/s13402-021-00599-9 · Cited by 51
Transporters at the Interface between Cytosolic and Mitochondrial Amino Acid Metabolism
Hewton, K. G., Johal, A. S., & Parker, S. J. (2021) · Metabolites · doi:10.3390/metabo11020112 · Cited by 52
“Activity of serine synthesis is important for normal development, as deletion of Phgdh causes embryonic lethality in part due to neurological defects [95].”
Background
PHGDH is required for germinal center formation and is a therapeutic target in MYC-driven lymphoma
D’Avola, A., Legrave, N. M., Tajan, M., Chakravarty, P., Shearer, R. L., King, H. W., Kluckova, K., Cheung, E. C., Clear, A. J., Gunawan, A. S., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci153436 · Cited by 47
“Deletion of the first enzyme of SSP pathway, Phgdh, does not prevent development, but Phgdh-deficient mice are born with severe neurological defects and die soon after birth.(46) To overcome these limitations, we first crossed Eμ-Myc mice with Rosa26-CreERT2/+mice,(47) which express a tamoxifen-inducible Cre recombina…”
Background
An essential role for de novo biosynthesis of L-serine in CNS development.
Furuya, S. (2008) · PubMed · Cited by 48
Self-citation
Glycolytic flux controls d -serine synthesis through glyceraldehyde-3-phosphate dehydrogenase in astrocytes
Suzuki, M., Sasabe, J., Miyoshi, Y., Kuwasako, K., Muto, Y., Hamase, K., Matsuoka, M., Imanishi, N., & Aiso, S. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1416117112 · Cited by 54
“Both serine enantiomers are deeply related to neurophysiology; L-serine is a neurotrophic factor essential for brain morphogenesis (31, 32), whereas D-serine is a prerequisite for glutamatergic neurotransmission mediated by synaptic NMDA receptors (13, 18, 33–35).”
Background
l-Serine protects mouse hippocampal neuronal HT22 cells against oxidative stress-mediated mitochondrial damage and apoptotic cell death
Kim, K. Y., Hwang, S., Park, S. Y., Kim, M. J., Jun, D. Y., & Kim, Y. H. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.07.018 · Cited by 47
A world of sphingolipids and glycolipids in the brain —Novel functions of simple lipids modified with glucose—
Hirabayashi, Y. (2012) · Proceedings of the Japan Academy Series B · doi:10.2183/pjab.88.129 · Cited by 48
Self-citation
Deoxysphingolipid precursors indicate abnormal sphingolipid metabolism in individuals with primary and secondary disturbances of serine availability
Ferreira, C. R., Goorden, S. M. I., Soldatos, A. G., Byers, H. M., der Vlugt, J. M. M. G.-V., Stet, F. S., Groden, C. A., van Karnebeek, C., Gahl, W. A., Vaz, F. M., et al. (2018) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2018.05.001 · Cited by 40
“Indeed, Phgdh knockout mice show decreased brain levels of serine-derived lipids, such as phosphatidylserine (PS), sphingomyelin, and ganglioside GD3 [3,4].”
Background
One Carbon Metabolism and Mammalian Pregnancy Outcomes
Cai, S., Quan, S., Yang, G., Ye, Q., Chen, M., Yu, H., Wang, G., Wang, Y., Zeng, X., & Qiao, S. (2020) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202000734 · Cited by 43
Serine biosynthesis by photorespiratory and non‐photorespiratory pathways: an interesting interplay with unknown regulatory networks
Ros, R., Cascales‐Miñana, B., Segura, J., Anoman, A. D., Toujani, W., Flores‐Tornero, M., Rosa‐Téllez, S., & Muñoz‐Bertomeu, J. (2012) · Plant Biology · doi:10.1111/j.1438-8677.2012.00682.x · Cited by 41
De novo serine synthesis regulates chondrocyte proliferation during bone development and repair
Stegen, S., Loopmans, S., Stockmans, I., Moermans, K., Carmeliet, P., & Carmeliet, G. (2022) · Bone Research · doi:10.1038/s41413-021-00185-7 · Cited by 38
d-Serine: The right or wrong isoform?
Fuchs, S. A., Berger, R., & de Koning, T. J. (2011) · Brain Research · doi:10.1016/j.brainres.2011.05.039 · Cited by 36
Cancer's sweet tooth for serine
Luo, J. (2011) · Breast Cancer Research · doi:10.1186/bcr2932 · Cited by 36
“Similar central nervous system disorders have been observed in PHGDH knockout mice [6].”
PHGDH supports liver ceramide synthesis and sustains lipid homeostasis
Kang, Y. P., Falzone, A., Liu, M., González‐Sánchez, P., Choi, B.-H., Coloff, J. L., Saller, J. J., Karreth, F. A., & DeNicola, G. M. (2020) · Cancer & Metabolism · doi:10.1186/s40170-020-00212-x · Cited by 32
“Whole animal PHGDH deletion is embryonic lethal in mice as a consequence of overall developmental retardation and brain defects (Yoshida et al., 2004).”
Background
A Serine Synthesis Defect Presenting With a Charcot-Marie-Tooth–Like Polyneuropathy
Méneret, A., Wiame, E., Marelli, C., Lenglet, T., SCHAFTINGEN, E. V., & Sedel, F. (2012) · Archives of Neurology · doi:10.1001/archneurol.2011.1526 · Cited by 36
“play an essential role in the central nervous system.(1) Three enzymes”
Background
Gene Expression Profiling Reveals Putative HOXA10 Downstream Targets in the Periimplantation Mouse Uterus
Vitiello, D., Pinard, R., & Taylor, H. S. (2008) · Reproductive Sciences · doi:10.1177/1933719108316911 · Cited by 36
Glycosignaling in neural stem cells: involvement of glycoconjugates in signal transduction modulating the neural stem cell fate
Yu, R. K., & Yanagisawa, M. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04710.x · Cited by 36
“2005) or 3-phosphoglycerate dehydrogenase-KO mice (Yoshida et al. 2004), seems to”
Background
Phosphoserine Phosphatase Is Expressed in the Neural Stem Cell Niche and Regulates Neural Stem and Progenitor Cell Proliferation
Nakano, I., Dougherty, J. D., Kim, K., Klement, I., Geschwind, D. H., & Kornblum, H. I. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0046 · Cited by 35
Impaired neurogenesis in embryonic spinal cord of Phgdh knockout mice, a serine deficiency disorder model
Kawakami, Y., Yoshida, K., Yang, J. H., Suzuki, T., Azuma, N., Sakai, K., Hashikawa, T., Watanabe, M., Yasuda, K., Kuhara, S., et al. (2008) · Neuroscience Research · doi:10.1016/j.neures.2008.12.002 · Cited by 32
Self-citation
Inactivation of the 3-phosphoglycerate dehydrogenase gene in mice: changes in gene expression and associated regulatory networks resulting from serine deficiency
Furuya, S., Yoshida, K., Kawakami, Y., Yang, J. H., Sayano, T., Azuma, N., Tanaka, H., Kuhara, S., & Hirabayashi, Y. (2008) · Functional & Integrative Genomics · doi:10.1007/s10142-007-0072-5 · Cited by 30
“Our preliminary histological examinations suggested that differentiation of neurons was impaired in the Phgdh KO embryos ( Yoshida et al. 2004 ).”
BackgroundMethodResultInfluentialSelf-citation
l-Serine induces sedative and hypnotic effects acting at GABAA receptors in neonatal chicks
Shigemi, K., Tsuneyoshi, Y., Hamasu, K., Li, H., Hayamizu, K., Denbow, D. M., & Furuse, M. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.09.036 · Cited by 28
“This idea is supported by the findings that neurons cannot maintain synthesis of serine-derived lipids without an external supply of L-serine (Mitoma et al., 1998b; Yoshida et al., 2004).”
Background
Serine and glycine physiology reversibly modulate retinal and peripheral nerve function
Lim, E. W., Fallon, R. J., Bates, C., Ideguchi, Y., Nagasaki, T., Handzlik, M. K., Joulia, E., Bonelli, R., Green, C. R., Ansell, B. R. E., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.07.021 · Cited by 27
Self-citation
Effects of L-serine ingestion on human sleep
Ito, Y., Takahashi, S., Shen, M., Yamaguchi, K., & Satoh, M. (2014) · SpringerPlus · doi:10.1186/2193-1801-3-456 · Cited by 28
“In knockout mice in whom 3-phosphoglycerate dehydrogenase (PHGDH) in the L-serine synthetic pathway is inactivated, abnormal brain morphogenesis, including microcephaly and absence of specific regions, and brain dysfunction occurs (Yoshida et al. 1980).”
Background
Neu–Laxova syndrome presenting prenatally with increased nuchal translucency and cystic hygroma: The utility of exome sequencing in deciphering the diagnosis
Bourque, D. K., Cloutier, M., Kernohan, K. D., Bareke, E., Grynspan, D., Michaud, J., & Boycott, K. M. (2019) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.61076 · Cited by 26
“One previous study has shown that murine knockout of Phgdh can lead to embryonic lethality (Yoshida et al., 2004).”
Background
Reduction of stratum corneum ceramides in Neu-Laxova syndrome caused by phosphoglycerate dehydrogenase deficiency
Takeichi, T., Okuno, Y., Kawamoto, A., Inoue, T., Nagamoto, E., Murase, C., Shimizu, E., Tanaka, K., Kageshita, Y., Fukushima, S., et al. (2018) · Journal of Lipid Research · doi:10.1194/jlr.p087536 · Cited by 26
“An analysis of membrane lipid components in embryonic tissues of conventional Phgdh KO mice show that l-serine deficiency resulting from Phgdh deletion leads to a drastic reduction of major sphingolipids (15, 20).”
Background
Increased mtDNA mutation frequency in oocytes causes epigenetic alterations and embryonic defects
Han, L., Chen, Y., Li, L., Ren, C., Wang, H., Wu, X., Ge, J., Shu, W., Chen, M., & Wang, Q. (2022) · National Science Review · doi:10.1093/nsr/nwac136 · Cited by 24
“These genes were selected based on their functions in embryogenesis and metabolism [34,35,37].”
Background
Beyond energy and growth: the role of metabolism in developmental signaling, cell behavior and diapause
Tippetts, T. S., Sieber, M., & Solmonson, A. (2023) · Development · doi:10.1242/dev.201610 · Cited by 25
INPP5K and SIL1 associated pathologies with overlapping clinical phenotypes converge through dysregulation of PHGDH
Hathazi, D., Cox, D., D’Amico, A., Tasca, G. A., Charlton, R., Carlier, R., Baumann, J., Kollipara, L., Zahedi, R. P., Feldmann, I., et al. (2021) · Brain · doi:10.1093/brain/awab133 · Cited by 23
A novel role of l-serine (l-Ser) for the expression of nuclear factor of activated T cells (NFAT)2 in receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis in vitro
Ogawa, T., Ishida‐Kitagawa, N., Tanaka, A., Μatsumoto, T., Hirouchi, T., Akimaru, M., Tanihara, M., Yogo, K., & Takeya, T. (2006) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-006-0705-0 · Cited by 22
“In fact, when phgdh was deleted in mice, early embryonic lethality was observed, with multiple developmental defects, particularly in the central nervous system [24].”
Background
Can small molecular inhibitors that stop de novo serine synthesis be used in cancer treatment?
McNamee, M., Michod, D., & Niklison-Chirou, M. V. (2021) · Cell Death Discovery · doi:10.1038/s41420-021-00474-4 · Cited by 23
Oral administration of l-serine reduces the locomotor activity of socially isolated rats
Shigemi, K., Tsuneyoshi, Y., Yamada, S., Kabuki, Y., Hayamizu, K., Denbow, D. M., & Furuse, M. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.10.068 · Cited by 22
A combined spectroscopic and molecular dynamic analysis of the inclusion behaviour of l-serine and β-cyclodextrin
Chakraborty, S., Karmakar, A., Goswami, T., Ghosh, P., & Mandal, A. (2020) · Journal of Molecular Liquids · doi:10.1016/j.molliq.2020.114447 · Cited by 21
Serum Metabolomics Study of Gliclazide-Modified-Release-Treated Type 2 Diabetes Mellitus Patients Using a Gas Chromatography–Mass Spectrometry Method
Zhou, Y., Hu, C., Zhao, X., Luo, P., Lu, J., Li, Q., Chen, M., Yan, D., Lu, X., Kong, H., et al. (2018) · Journal of Proteome Research · doi:10.1021/acs.jproteome.7b00866 · Cited by 21
Dietary serine supplementation: Friend or foe?
Jiang, J., Li, B., He, W., & Huang, C. (2021) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2021.08.011 · Cited by 21
The impact of amino acid metabolism on adult neurogenesis.
Guo, Y., Luo, X., & Guo, W.-X. (2023) · Biochemical Society Transactions · doi:10.1042/bst20220762 · Cited by 18
Myotube growth is associated with cancer-like metabolic reprogramming and is limited by phosphoglycerate dehydrogenase
Stadhouders, L. E. M., Smith, J. A. B., Gabriel, B. M., Verbrugge, S. A. J., Hammersen, T. D., Kolijn, D., Vogel, I. S. P., Mohamed, A. D., de Wit, G. M. J., Offringa, C., et al. (2023) · Experimental Cell Research · doi:10.1016/j.yexcr.2023.113820 · Cited by 19
Deletion of PHGDH in adipocytes improves glucose intolerance in diet-induced obese mice
Okabe, K., Usui, I., Yaku, K., Hirabayashi, Y., Tobe, K., & Nakagawa, T. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.08.180 · Cited by 19
Self-citation
Positive regulation of promoter activity of human 3-phosphoglycerate dehydrogenase (PHGDH) gene is mediated by transcription factors Sp1 and NF-Y
Jun, D. Y., Park, H. S., Lee, J. Y., Baek, J. Y., Park, H.-K., Fukui, K., & Kim, Y. H. (2008) · Gene · doi:10.1016/j.gene.2008.02.018 · Cited by 17
l ‐Serine deficiency caused by genetic P hgdh deletion leads to robust induction of 4E‐ BP 1 and subsequent repression of translation initiation in the developing central nervous system
Sayano, T., Kawakami, Y., Kusada, W., Suzuki, T., Kawano, Y., Watanabe, A., Takashima, K., Arimoto, Y., Esaki, K., Wada, A., et al. (2013) · FEBS Journal · doi:10.1111/febs.12146 · Cited by 17
Self-citation
Mouse 3-phosphoglycerate dehydrogenase gene: genomic organization, chromosomal localization, and promoter analysis
Mitoma, J., Furuya, S., Shimizu, M., Shinoda, Y., Yoshida, K., Azuma, N., Tanaka, H., Suzuki, Y., & Hirabayashi, Y. (2004) · Gene · doi:10.1016/j.gene.2004.03.015 · Cited by 17
Self-citation
Serine metabolism in aging and age-related diseases
Shan, S., & Hoffman, J. M. (2024) · GeroScience · doi:10.1007/s11357-024-01444-1 · Cited by 15
“In mice, the deletion of PHGDH, the first enzyme in the SSP, results in severe neurological defects and early postnatal death [121].”
Adaptive response to l ‐serine deficiency is mediated by p38 MAPK activation via 1‐deoxysphinganine in normal fibroblasts
Sayano, T., Kawano, Y., Kusada, W., Arimoto, Y., Esaki, K., Hamano, M., Udono, M., Katakura, Y., Ogawa, T., Kato, H., et al. (2016) · FEBS Open Bio · doi:10.1002/2211-5463.12038 · Cited by 15
Self-citation
The integrated stress response fine-tunes stem cell fate decisions upon serine deprivation and tissue injury
Novak, J. S. S., Polak, L., Baksh, S. C., Barrows, D., Schernthanner, M., Jackson, B. T., Thompson, E. A. N., Gola, A., Abdusselamoglu, M. D., Bonny, A. R., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.05.010 · Cited by 17
Inhibition of Phosphoglycerate Dehydrogenase Radiosensitizes Human Colorectal Cancer Cells under Hypoxic Conditions
Gucht, M. V. D., Dufait, I., Kerkhove, L., Corbet, C., de Mey, S., Jiang, H., Ka, L. L., Gevaert, T., Féron, O., & Ridder, M. D. (2022) · Cancers · doi:10.3390/cancers14205060 · Cited by 15
“It must be mentioned that observations in PHGDH-deficient mice have been made that show abnormalities during embryonic development by malformations in the central nervous system [40].”
Background
Enhanced vulnerability to oxidative stress and induction of inflammatory gene expression in 3‐phosphoglycerate dehydrogenase‐deficient fibroblasts
Hamano, M., Haraguchi, Y., Sayano, T., Zyao, C., Arimoto, Y., Kawano, Y., Moriyasu, K., Udono, M., Katakura, Y., Ogawa, T., et al. (2018) · FEBS Open Bio · doi:10.1002/2211-5463.12429 · Cited by 14
Self-citation
Phosphoglycerate dehydrogenase positively regulates the proliferation of chicken muscle cells
Wang, H., Hu, M., Ding, Z., Zhou, X., Yang, S., Shen, Z., Yan, F., & Zhao, A. (2022) · Poultry Science · doi:10.1016/j.psj.2022.101805 · Cited by 13
“PHGDH catalyzes the first step in the synthesis of serine, a necessary precursor for the synthesis of various cell proliferation-related biomolecules (Yoshida et al., 2004).”
Background
l-Serine-O-phosphate in the central nervous system
Antflick, J. E., Vetiska, S., Baizer, J. S., Yao, Y., Baker, G. B., & Hampson, D. R. (2009) · Brain Research · doi:10.1016/j.brainres.2009.08.087 · Cited by 13
Dietary L-serine modifies free amino acid composition of maternal milk and lowers the body weight of the offspring in mice
NAGAMACHI, S., Nishigawa, T., Takakura, M., Ikeda, H., Kodaira, M., Yamaguchi, T., Chowdhury, V. S., Yasuo, S., & Furuse, M. (2017) · Journal of Veterinary Medical Science · doi:10.1292/jvms.17-0577 · Cited by 13
“This pathway is essential for normal embryonic development, especially for brain morphogenesis [33].”
Background
Proteomic Profiling of the Insoluble Pellets of the Transected Rat Spinal Cord
Yan, X., Liu, T., Yang, S., Ding, R., Liu, Y., Zhang, X., Que, H., Wei, K., Luo, Z., & Liu, S. (2009) · Journal of Neurotrauma · doi:10.1089/neu.2008.0533 · Cited by 13
“Disruption of the PHGDH gene can cause severe neurodevelopmental defects (Yoshida et al., 2004).”
Functional analysis of mouse 3‐phosphoglycerate dehydrogenase (Phgdh) gene promoter in developing brain
Shimizu, M., Furuya, S., Shinoda, Y., Mitoma, J., Okamura, T., Miyoshi, I., Kasai, N., Hirabayashi, Y., & Suzuki, Y. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20102 · Cited by 13
“Targeted disruption of the mouse Phgdh gene culminated in embryonic lethality, accompanied by overall developmental retardation and striking defects of the brain (Yoshida et al., 2004).”
BackgroundSelf-citation
Hepatocyte-Specific Phgdh-Deficient Mice Culminate in Mild Obesity, Insulin Resistance, and Enhanced Vulnerability to Protein Starvation
Hamano, M., Esaki, K., Moriyasu, K., Yasuda, T., Mohri, S., Tashiro, K., Hirabayashi, Y., & Furuya, S. (2021) · Nutrients · doi:10.3390/nu13103468 · Cited by 12
“L-Serine (Ser), a nutritionally dispensable amino acid, serves as an indispensable metabolite essential for mammalian fetal development [1,2].”
BackgroundSelf-citation
Selective upregulation of 3-phosphoglycerate dehydrogenase (Phgdh) expression in adult subventricular zone neurogenic niche
Kinoshita, M. O., Shinoda, Y., Sakai, K., Hashikawa, T., Watanabe, M., Machida, T., Hirabayashi, Y., & Furuya, S. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.02.001 · Cited by 12
Self-citation
Clinical histopathology and pathogenesis of macular telangiectasia type 2
Ntentakis, D. P., Ntentaki, A. M., Delavogia, E., Sakuno, G., Correa, V., Efstathiou, N. E., Aronow, M. E., Chew, E. Y., Miller, J. W., & Vavvas, D. G. (2025) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2025.101401 · Cited by 13
Phgdh serves a protective role in Il‑1β induced chondrocyte inflammation and oxidative‑stress damage
Huang, H., Liu, K., Ou, H., Qian, X., & Wan, J. (2021) · Molecular Medicine Reports · doi:10.3892/mmr.2021.12058 · Cited by 11
Requirement of the expression of 3-phosphoglycerate dehydrogenase for traversing S phase in murine T lymphocytes following immobilized anti-CD3 activation
Jun, D. Y., Taub, D. D., Chrest, F. J., & Kim, Y. H. (2013) · Cellular Immunology · doi:10.1016/j.cellimm.2013.12.003 · Cited by 9
Expression of l-Serine Biosynthetic Enzyme 3-Phosphoglycerate Dehydrogenase (Phgdh) and Neutral Amino Acid Transporter ASCT1 Following an Excitotoxic Lesion in the Mouse Hippocampus
Jeon, G. S., Choi, D.-H., Lee, H. N., Kim, D. W., Chung, C. K., & Cho, S. S. (2008) · Neurochemical Research · doi:10.1007/s11064-008-9831-5 · Cited by 9
“Further, the targeted disruption of the Phgdh gene in mice resulted in embryonic lethality coupled with striking defects and retardation of brain development [34].”
Background

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: Furuya, Shigeki
Mitoma, Junya
Watanabe, Masahiko
Tanaka, Hideyuki
Itohara, Shigeyoshi
Hirabayashi, Yoshio
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2004-01
Volume: 279
Issue: 5
Pages: 3573-3577
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.c300507200
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: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 6108 d)
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Targeted Disruption of the Mouse 3-Phosphoglycerate Dehydrogenase Gene Causes Severe Neurodevelopmental Defects and Results in Embryonic Lethality

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks