Defective Thymocyte Maturation in p44 MAP Kinase (Erk 1) Knockout Mice
Abstract
The p42 and p44 mitogen-activated protein kinases (MAPKs), also called Erk2 and Erk1, respectively, have been implicated in proliferation as well as in differentiation programs. The specific role of the p44 MAPK isoform in the whole animal was evaluated by generation of p44 MAPK-deficient mice by homologous recombination in embryonic stem cells. The p44 MAPK –/– mice were viable, fertile, and of normal size. Thus, p44 MAPK is apparently dispensable and p42 MAPK (Erk2) may compensate for its loss. However, in p44 MAPK −/− mice, thymocyte maturation beyond the CD4 + CD8 + stage was reduced by half, with a similar diminution in the thymocyte subpopulation expressing high levels of T cell receptor (CD3 high ). In p44 MAPK −/− thymocytes, proliferation in response to activation with a monoclonal antibody to the T cell receptor in the presence of phorbol myristate acetate was severely reduced even though activation of p42 MAPK was more sustained in these cells. The p44 MAPK apparently has a specific role in thymocyte development.
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During development, ERK1 and ERK2 have divergent functions since ERK1 null mice are grossly viable and fertile while ERK2 null mice are embryonic lethal.
“During development, ERK1 and ERK2 have divergent functions since ERK1 null mice are grossly viable and fertile while ERK2 null mice are embryonic lethal7–9.”
From Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse (2019) · cites this paper as [9]
Erk1 KO mice do not show significant developmental changes.
“Consistent with this hypothesis, previous reports have indicated significant developmental changes by genetic abrogation of Erk2222324, but not in Erk1 KO mice25.”
From Transient blockade of ERK phosphorylation in the critical period causes autistic phenotypes as an adult in mice (2015) · cites this paper as [25]
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- Authors
- Pagès, G., Guérin, S., Grall, D., Bonino, F., Smith, A., Anjuere, F., Auberger, P., & Pouysségur, J.
- Affiliations
- Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Centre A. Lacassagne, 33 Avenue de Valombrose, 06189 Nice, France.
- Faculté de Medecine, INSERM U364 and CJF 96.05, Avenue de Valombrose, 06107 Nice, France.
- Centre National de la Recherche Scientifique (FR)
- University of Edinburgh (GB)
- Inserm (FR)
- Venue
- Science
- Published
- 1999-11-12
- Volume
- 286
- Issue
- 5443
- Pages
- 1374-1377
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1967400782
- Cited by
- 654
- References
- 23
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 10 · 2022: 13 · 2021: 14 · 2020: 12 · 2019: 12 · 2018: 16 · 2017: 26 · 2016: 19 · 2015: 29 · 2014: 23 · 2013: 22 · 2012: 48
- FWCI
- 8.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- ERK1, ERK2, p42 MAP kinase, T cell development, knockout mice, T cell receptor signaling, thymocyte proliferation, CD4+CD8+ thymocytes, compensatory function
- MeSH terms
- Animals, Antibodies, Monoclonal, Cell Differentiation, Cell Division, Cells, Cultured, DNA, Enzyme Activation, Isoenzymes, Phosphorylation, Polymorphism, Restriction Fragment Length, Tetradecanoylphorbol Acetate, Thymus Gland, Antigens, CD, T-Lymphocyte Subsets, Receptors, Antigen, T-Cell, alpha-beta, CD3 Complex, Mice, Knockout, Gene Targeting, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 3, Mice
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