Replicative advantage and tissue-specific segregation of RR mitochondrial DNA between C57BL/6 and RR heteroplasmic mice

To investigate the interactions between mtDNA and nuclear genomes, we produ ced heteroplasmic maternal lineages by transferring the cytoplasts between the embryos of two mouse strains, C57BL/6 (B6) and RR. A total of 43 differ ent nucleotides exist in the displacement-loop (D-loop) region of mtDNA bet ween B6 and RR. Heteroplasmic embryos were reconstructed by electrofusion u sing a blastomere from a two-cell stage embryo of one strain and an enuclea ted blastomere fr-om a two-cell stage embryo of the other strain. Equivalen t volumes of both types of mtDNAs were detected in blastocyst stage embryos . However, the mtDNA from the RR strain became biased in the progeny, regar dless of the source of the nuclear genome. The RR mtDNA population was very high in most of the tissues examined but was relatively low in the brain a nd the heart. An age-related increase of RR mtDNA was also observed in the blood. The RR mtDNAs in the reconstructed embryos and in the embryos collec ted from heteroplasmic mice showed. a different segregation pattern during early embryonic development. These results suggest that the RR mtDNA has a replicative advantage over B6 mtDNA during embryonic development and differ entiation, regardless of the type of nuclear genome.