Leber hereditary optic neuropathy (LHON) is a disorder of the retina and optic nerve associated with a mutation in mitochondrial DNA (mtDNA). Developing therapies for disorders caused by mtDNA mutations is challenging because of a lack of suitable animal models. 

Researchers in the journal PNAS. introduced human mtDNA containing the LHON mutation directly into mitochondria of mouse zygotes using a virus. The zygotes developed into transgenic mice that expressed the mutant gene in their optic nerves and retinas.

Breeding transgenic females with nontransgenic males for several generations produced more than 200 transgenic mice exhibiting hallmark signs of LHON, including progressive vision loss, thinning of the retina, and severe optic nerve atrophy.

Transgenic mice also exhibited increased oxidative stress and decreased cellular respiration in the optic nerve, compared with control mice. The authors were able to partially reverse the vision loss by injecting a virus containing wild-type human mtDNA into the eyes of the transgenic mice.

The authors suggest that their method could be adapted to create mouse models of other disorders caused by mtDNA mutations, enabling tests of treatments for such disorders. The results also suggest that gene therapy might be a promising approach to treat such disorders.

http://www.pnas.org/content/early/2015/09/30/1506129112