Mutations of mitochondrial DNA are a significant cause of neuromuscular disease. Pathological mutant mitochondrial DNA has been studied in control nuclear backgrounds. These experiments entailed transfer of patient-derived mitochondria to ρ0 cells that lack mtDNA. A limitation of these studies has been the fact that the control nuclear backgrounds were unrelated to the affected tissues of patients. Therefore a rhabdomyosarcoma cell line that has 'muscle-like' properties was tested to determine whether it could be depleted of mtDNA. A human rhabdomyosarcoma cell line was treated with the DNA intercalating dye ethidium bromide (3,8-diamino-5-ethyl-6-phenylphenanthridinium bromide) for 45 days. The treatment induced complete and permanent loss of mitochondrial DNA (ρ0) in the rhabdomyosarcoma cells, as mtDNA remained undetectable after 8 months of growth in medium without drug. Crucially, the rhabdomyosarcoma ρ0 cells retained the ability to differentiate into myotubes with expression of muscle specific isoenzymes. The rhabdomyosarcoma ρ0 cell line provides a model system for studying pathological mutant mtDNA in cells that more closely resemble human muscle than the hitherto available human ρ0 cell lines. Copyright (C) 2000 Elsevier Science B.V.
- ρ cell
- Muscle differentiation