| First Author | Humble MM | Year | 2013 |
| Journal | Hum Mol Genet | Volume | 22 |
| Issue | 5 | Pages | 1017-25 |
| PubMed ID | 23197651 | Mgi Jnum | J:192568 |
| Mgi Id | MGI:5465384 | Doi | 10.1093/hmg/dds506 |
| Citation | Humble MM, et al. (2013) Polg2 is essential for mammalian embryogenesis and is required for mtDNA maintenance. Hum Mol Genet 22(5):1017-25 |
| abstractText | Mammalian mitochondrial DNA (mtDNA) is replicated by the heterotrimeric Pol gamma 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. |
