Defects in mitochondrial DNA (mtDNA) are associated with human degenerative diseases, aging, and cancer. One difficulty in creating animal models for these diseases has been an inability to achieve stable transmission of exogenous mitochondrial DNA.
Inouye et al. fused vesicles derived from the brains of aged mice with a cell line whose mitochondria lacked DNA. Several such "cybrids" containing mtDNA deletion mutations were fused with mouse embryos and implanted into female mice. The resulting offspring contained around 5 to 40% mutant mitochondrial DNA, and the females were able to transmit the mutant DNA to their progeny. Whilst these mice demonstrated abnormalities distinct from those seen in human diseases, the mice did have abnormal mitochondria in their muscles. Most of the mice with large proportions of mutant mitochondrial DNA died of renal failure within 200 days, a problem rarely seen in human mitochondrial disorders. However, these mice have the potential to yield insights into the underlying mechanisms of pathology in human disorders. -- BJ