Early embryonic lethality caused by targeted disruption of the mouse PHGPx gene
Abstract
Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is the only known intracellular antioxidant enzyme that can directly reduce lipid hydroperoxide in membrane. Mitochondrial and non-mitochondrial PHGPx and sperm nuclei GPx are transcribed from one gene by alternative transcription using different first exons Ia and Ib, respectively. To examine the role of PHGPx in development, we generated mice deficient in PHGPx by a targeted disruption of all exons of the PHGPx gene. Heterozygotes are viable, fertile, and appear normal, despite having decreased levels of three types of PHGPx mRNA and protein. Embryos homozygous for PHGPx-null die between 7.5 and 8.5 days post coitum (dpc), probably developing distal apoptosis. We examined the expression of PHGPx in mouse embryos using immunohistochemical analysis with anti-PHGPx mAb. The expression of PHGPx was detected in the embryonic ectoderm and the yolk sac membrane at 7.5dpc. The results demonstrated that PHGPx is expressed in early gastrulation stage at 7.5dpc and that the expression of PHGPx was essential for normal mouse development.
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Gpx4−/− mice display embryonic lethality with complete penetrance.
“Gpx4−/− mice display embryonic lethality with complete penetrance [547, 550, 587, 588].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [587]
Gpx4 knockout in mice causes embryonic lethality between E7.5 and E8.5, indicating Gpx4 is essential for mouse development.
“Knockout of Gpx4 in mice caused embryonic lethality between E7.5 and E8.5, indicating an essential role of Gpx4 in mouse development [42, 43].”
From Ferroptosis: Death by Lipid Peroxidation (2016) · cites this paper as [42]
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References 30 · Cited by 357
- Authors
- Imai, H., Hirao, F., Sakamoto, T., Sekine, K., Mizukura, Y., Saito, M., Kitamoto, T., Hayasaka, M., Hanaoka, K., & Nakagawa, Y.
- Affiliations
- Kitasato University (JP)
- Corresponding author
- Nakagawa, Yasuhito
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2003-05
- Volume
- 305
- Issue
- 2
- Pages
- 278-286
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W1969436148
- Cited by
- 357
- References
- 30
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 22 · 2023: 23 · 2022: 30 · 2021: 25 · 2020: 17 · 2019: 19 · 2018: 15 · 2017: 12 · 2016: 18 · 2015: 15 · 2014: 15 · 2013: 9 · 2012: 9
- FWCI
- 6.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ono Medical Research Foundation
- Uehara Memorial Foundation
- Ministry of Education, Culture, Sports, Science and Technology
- Kitasato University
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- phospholipid hydroperoxide glutathione peroxidase, embryonic lethality, knockout mice, alternative transcription, antioxidant enzymes, apoptosis, gastrulation, embryonic development, yolk sac
- MeSH terms
- Phospholipid Hydroperoxide Glutathione Peroxidase, Animals, Cells, Cultured, Embryo, Mammalian, Female, Embryonic and Fetal Development, Genes, Lethal, Genotype, Glutathione Peroxidase, Heterozygote, Homozygote, Phenotype, Pregnancy, RNA, Messenger, Tissue Distribution, Mice, Knockout, Gene Targeting, Embryonic Development, Mice
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