G7731A mutation in mouse mitochondrial tRNALys regulates late-onset disorders in transmitochondrial mice

We previously generated mito-mice-tRNALys7731 as a model for primary prevention of mitochondrial diseases. These mice harbour a G7731A mtDNA mutation in the tRNALys gene, but express only muscle weakness and short body length by four months. Here, we examined the effects of their aging on metabolic and histologic features. Unlike young mito-mice-tRNALys7731, aged mito-mice-tRNALys7731 developed muscle atrophy, renal failures, and various metabolic abnormalities, such as lactic acidosis and anemia, characteristic of patients with mitochondrial diseases. These observations provide convincing evidence that the respiration defects induced by high G7731A mtDNA levels cause these late-onset disorders that are relevant to mitochondrial diseases.