Evaluation of Gastrointestinal mtDNA Depletion in Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare disease characterized by severe gastro-intestinal (GI) dysmotility caused by mutations in the thymidine phosphorylase gene. Thymidine phosphorylase (TP) is involved in the control of the pyrimidine nucleoside pool of the cell. Reduced TP activity induces nucleotide pool imbalances that in turn affect both the rate and fidelity of mtDNA replication, leading to multiple deletions and depletion of mtDNA. By using laser capture microdissection and quantitative real-time-polymerase chain reaction technique, we showed that depletion of mitochondrial DNA (mtDNA) is the most prominent molecular defect in the gut wall of MNGIE patients. Depletion affects severely the smooth muscle cells of muscularis propria and the skeletal muscle component of the upper esophagus, while ganglion cells of the myenteric plexus show only a milder mtDNA reduction.
Key wordsMitochondrial disease mtDNA depletion mtDNA deletion CPEO
The authors wish to thank Doctor Martina Leopizzi and Doctor Maurizia Orlandi for technical assistance. This work was supported by Fondazione Giuseppe Tomasello and Associazione Serena Tallarico per i Giovani nel Mondo.
- 7.Cossarizza, A., Riva, A., Pinti, M., Ammannato, S., Fedeli, P., Mussini, C., et al. (2003) Increased mitochondrial DNA content in peripheral blood lymphocytes from HIV-infected patients with lipodystrophy. Antivir Ther. 8, 51–57.Google Scholar
- 8.Gilbert, M.T., Haselkorn, T., Bunce, M., Sanchez, J.J., Lucas, S.B., Jewell, L.D., et al. (2007) The isolation of nucleic acids from fixed, paraffin-embedded tissues—which methods are useful when? PLoS ONE. 2, p. e537.Google Scholar