Characterization of POLG in Mitochondrial Disease

Abstract The replication of mitochondrial DNA (mtDNA) relies on Polymerase γ (POLγ), which comprises a catalytic subunit (POLγA), encoded by POLG, and two accessory subunits (POLγB), encoded by POLG2. Mutations in POLG are a major cause of mitochondrial diseases. I studied three mouse models of POLG-related disorders to investigate: (i) the Mendelian distribution of the genotypes by standard PCR, (ii) the quantity and quality of mtDNA in different tissues by real time and long-range PCR, (iii) the amount of POLγ subunits by western blot. One model was embryonic lethal, while the others were viable and born at the expected Mendelian ratio. MtDNA content was reduced in some tissues at 3 months of age, without accumulation of multiple deletions. Similarly, POLγA, but not POLγB, was reduced in some tissues of mutants. Overall, my results indicate that POLG mouse models can be used to dissect the pathogenesis of POLG-related disorders.