Isolation and microinjection of somatic cell-derived mitochondria and germline heteroplasmy in transmitochondrial mice

At present, there are no means for creation of relevant animal models of hu man mitochondrial DNA (mtDNA)-based diseases in a directed fashion. As an i nitial step towards this end, we have developed a microinjection technique for transfer of isolated, viable mitochondria between two mouse species. Pr eviously, we reported detection, by nested PCR with species-specific primer sets, of Mus spretus mtDNA in Mus musculus domesticus blastocysts followin g zygote microinjection and culture. We now report the production of transm itochondrial founder mice, and germline transmission of the heteroplasmic s tate in a maternal lineage. Heteroplasmic mice produced by this technique w ill be useful in the study of mitochondrial dynamics and may hasten the cre ation of animal models of human mtDNA-based diseases.