Heteroplasmy between wild type mitochondrial DNA variants is detrimental and shorten life span

We evaluated here the physiological consequences of the generation of heteroplasmic embryos by mix of two wild type mtDNAs in the same zygote. In this animal model, mtDNA heteroplasmy is actively combated during germ-line transmission, embryonic development and somatic life of most differentiated cells. mtDNA heteroplasmy alone, even when both mtDNA types are individually non-pathogenic, causes a disease affecting mainly those tissues that are not able to reduce their heteroplasmy: heart, lung and skeletal muscle. Overall design: Transcriptome analysis of 12-weeks-old conplastic mice (BL/6^C57 and BL/6^NZB) versus heteroplasmic mice (BL/6^C57-NZB) in heart tissue. We generated heteroplasmic mice by electro-fusion of an embryo and an enucleated embryo, using two conplastic mouse strains: nuclear genome from C57BL/6JOlaHsd strain and mtDNA either of NZB/OlaHsd (BL/6^NZB) or C57BL/6JOlaHsd mtDNA (BL/6^C57).