Polg2 is essential for mammalian embryogenesis and is required for mtDNA maintenance
Open accessAbstract
Mammalian mitochondrial DNA (mtDNA) is replicated by the heterotrimeric Pol γ comprised of a single catalytic subunit, encoded by Polg, and a homodimeric accessory subunit encoded by the Polg2 gene. While the catalytic subunit has been shown to be essential for embryo development, genetic data regarding the accessory subunit are lacking in mammalian systems. Here, we describe the generation of heterozygous (Polg2(+/-)) and homozygous (Polg2(-/-)) knockout (KO) mice. Polg2(+/-) mice are haplosufficient and develop normally with no discernable difference in mitochondrial function through 2 years of age. In contrast, the Polg2(-/-) is embryonic lethal at day 8.0-8.5 p.c. with concomitant loss of mtDNA and mtDNA gene products. Electron microscopy shows severe ultra-structural defects and loss of organized cristae in mitochondria of the Polg2(-/-) embryos as well as an increase in lipid accumulation compared with both wild-type (WT) and Polg2(+/-) embryos. Our data indicate that Polg2 function is critical to mammalian embryogenesis and mtDNA replication, and that a single copy of Polg2 is sufficient to sustain life.
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A complete POLG2 knock-out is embryonic lethal in mice, but the heterozygous knockout (+/−) mouse has a normal phenotype.
“A complete POLG2 knock-out is embryonic lethal in mice, but the heterozygous knockout (+/−) mouse has a normal phenotype (Humble et al., 2013).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Humble et al., 2013
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- Authors
- Humble, M. M., Young, M. J., Foley, J. F., Pandiri, A. R., Travlos, G. S., & Copeland, W. C.
- Affiliations
- National Institutes of Health (US)
- Laboratory of Molecular Genetics (PL)
- Experimental Pathology Laboratories (US)
- Corresponding author
- Copeland, William C.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-11-29
- Volume
- 22
- Issue
- 5
- Pages
- 1017-1025
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC3561914
- OpenAlex
- W2163141588
- Cited by
- 78
- References
- 39
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 7 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 6 · 2019: 9 · 2018: 5 · 2017: 5 · 2016: 8 · 2015: 5 · 2014: 9 · 2013: 2
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Molecular Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Environmental Health Sciences (ES 065080, ES-065078)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- POLG2, mitochondrial DNA maintenance, mitochondrial DNA replication, embryonic lethality, knockout mice, mitochondrial ultrastructure, lipid accumulation, mammalian embryogenesis
- MeSH terms
- DNA Polymerase gamma, Animals, DNA-Directed DNA Polymerase, DNA Replication, DNA, Mitochondrial, Heterozygote, Humans, Mitochondria, Mice, Knockout, Embryonic Development, Mice
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