Delayed embryonic lethality in mice lacking protein phosphatase 2A catalytic subunit Cα
Open accessAbstract
Protein phosphatase 2A (PP2A) is a multimeric enzyme, containing a catalytic subunit complexed with two regulatory subunits. The catalytic subunit PP2A C is encoded by two distinct and unlinked genes, termed Calpha and Cbeta. The specific function of these two catalytic subunits is unknown. To address the possible redundancy between PP2A and related phosphatases as well as between Calpha and Cbeta, the Calpha subunit gene was deleted by homologous recombination. Homozygous null mutant mice are embryonically lethal, demonstrating that the Calpha subunit gene is an essential gene. As PP2A exerts a range of cellular functions including cell cycle regulation and cell fate determination, we were surprised to find that these embryos develop normally until postimplantation, around embryonic day 5.5/6.0. While no Calpha protein is expressed, we find comparable expression levels of PP2A C at a time when the embryo is degenerating. Despite a 97% amino acid identity, Cbeta cannot completely compensate for the absence of Calpha. Degenerated embryos can be recovered even at embryonic day 13.5, indicating that although embryonic tissue is still capable of proliferating, normal differentiation is significantly impaired. While the primary germ layers ectoderm and endoderm are formed, mesoderm is not formed in degenerating embryos.
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The Ppp2ca (Cα) knockout mouse is embryonically lethal, which implies a lack of redundancy between Cα and Cβ isoforms.
“Despite Cα and Cβ sharing 97% amino acid identity, the Ppp2ca (Cα) knockout (KO) mouse is embryonically lethal [9], implying a lack of redundancy between these isoforms.”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [9]
At E6.5, gastrulation could not be initiated, resulting in absence of differentiated mesoderm and Wnt target gene markers Goosecoid and Brachyury in Cα-/- embryos.
“At this stage, gastrulation could not be initiated, resulting in absence of differentiated mesoderm and accompanying Wnt target gene markers, Goosecoid and Brachyury in Cα -/-embryos [9].”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [9]
Constitutive homozygous knockout of Ppp2ca in mice resulted in embryonic lethality, with premature death and degeneration starting at E6.5.
“Constitutive, homozygous KO of Ppp2ca in mice resulted in embryonic lethality, with premature death and degeneration starting at embryonic day E6.5.”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [9]
Homozygous deletion of PPP2R1A and PPP2CA in mice is embryonically lethal.
“More importantly, knockout (KO) studies in mice have revealed that the homozygous deletion of PPP2R1A and PPP2CA is embryonically lethal [ 36 – 38 ].”
From Targeting PP2A in cancer: an underrated option (2025) · cites this paper as [38]
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- Authors
- Götz, J., Probst, A., Ehler, E., Hemmings, B., & Kues, W.
- Affiliations
- University of Basel (CH)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1998-10-13
- Volume
- 95
- Issue
- 21
- Pages
- 12370-12375
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC22838
- OpenAlex
- W2074455749
- Cited by
- 220
- References
- 32
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 5 · 2017: 7 · 2016: 7 · 2015: 8 · 2014: 11 · 2013: 10 · 2012: 10
- FWCI
- 3.72
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- protein phosphatase 2A, embryonic lethality, gene deletion, mesoderm formation, germ layer differentiation, cell fate determination, cell cycle regulation, functional redundancy, phosphatase
- MeSH terms
- Animals, Base Sequence, Catalysis, Cell Differentiation, Cell Division, Embryo, Mammalian, Embryonic and Fetal Development, Genes, Lethal, Immunohistochemistry, Phosphoprotein Phosphatases, DNA Primers, Mice, Knockout, Mice, Protein Phosphatase 2
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