With the advancement of various gene transfer technologies, establishment of mitochondrial engineering and transfer as viable techniques to genetically engineer animal models paradoxically lags behind other genetic engineering technologies. The sheer number of mitochondrial DNA (mtDNA) copies per cell and the lack of demonstrable recombination in mtDNA necessitate different approaches to conventional transgenesis-based techniques. Initially, heteroplasmic mice were created to explore disease pathogenesis and mitochondrial dynamics in an in vivo system. Here, we describe production of transmitochondrial mice harboring foreign mitochondrial genomes and related targeting approaches for modifying mitochondrial gene function. Animal modeling and the procedures for mitochondrial transfer will be of considerable importance in gaining understanding of specific mitochondrial mutations and may well lead to novel strategies and therapies for human diseases influenced by mtDNA mutation.
