Mouse embryos containing DNA from three animals may not survive gestation, and those that do could go on to develop reproductive problems — a finding with potential implications for a proposed human therapy.

Energy-producing cell organelles called mitochondria carry their own DNA, which when mutated can cause disease. Mitochondrial-replacement therapy is being developed to prevent the inheritance of such diseases and involves the replacement of the organelles with donor ones, resulting in embryos with DNA from three people. To look for potential incompatibilities between the mitochondrial and nuclear genomes, a team led by Shoukhrat Mitalipov at the Oregon Health and Science University in Portland replaced the mitochondria in fertilized eggs from one subspecies of mouse with those from another subspecies.

Embryos containing nuclear DNA from Mus mus domesticus and mitochondrial DNA (mtDNA) from Mus mus musculus produced healthy female progeny and males with reduced fertility. However, most of the embryos containing nuclear DNA from M. m. musculus and mtDNA from M. m. domesticus were aborted or stillborn.

Should mitochondrial-replacement therapy reach the clinic, the authors recommend selecting donors with similar mtDNA to recipients.

Cell Metab. http://doi.org/bmn5 (2016)