Targeted deletion of p97 (VCP/CDC48) in mouse results in early embryonic lethality
Abstract
The highly conserved AAA ATPase p97 (VCP/CDC48) has well-established roles in cell cycle progression, proteasome degradation and membrane dynamics. Gene disruption in Saccromyces cerevisiae, Drosophila melanogaster and Trypanosoma brucei demonstrated that p97 is essential in unicellular and multicellular organisms. To explore the requirement for p97 in mammalian cell function and embryogenesis, we disrupted the p97 locus by gene targeting. Heterozygous p97+/- mice were indistinguishable from their wild-type littermates, whereas homozygous mutants did not survive to birth and died at a peri-implantation stage. These results show that p97 is an essential gene for early mouse development.
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p97/VCP gene disruption causes early embryonic lethality in mice.
“Its gene disruption causes early embryonic lethality in mice, highlighting the importance of maintaining proteostasis during embryogenesis [170].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [170]
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- Authors
- Müller, J. M. M., Deinhardt, K., Rosewell, I., Warren, G., & Shima, D. T.
- Affiliations
- Cancer Research UK (GB)
- Yale University (US)
- Corresponding author
- Shima, D.T.
- ORCID
- Deinhardt, K.
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 354
- Issue
- 2
- Pages
- 459-465
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2051152369
- Cited by
- 133
- References
- 35
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 7 · 2021: 12 · 2020: 5 · 2019: 8 · 2018: 11 · 2017: 6 · 2016: 9 · 2015: 10 · 2014: 7 · 2013: 6 · 2012: 14
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Cancer Research UK
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- VCP, Cdc48, AAA+ ATPase, embryonic lethality, gene targeting, mouse mutants, peri-implantation development, embryonic development, essential genes, proteasomal degradation, membrane dynamics
- MeSH terms
- Valosin Containing Protein, Adenosine Triphosphatases, Animals, Breeding, Female, Heterozygote, Homozygote, Male, Mice, Inbred CBA, Mice, Inbred C57BL, Nuclear Proteins, Embryo Implantation, Gene Deletion, Mice, Knockout, Gene Targeting, Cell Cycle Proteins, Embryo Loss, Mice, Embryonic Stem Cells
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