Accumulation of pathogenic DeltamtDNA induced deafness but not diabetic phenotypes in mito-mice.

Mito-mice carrying various proportions of deletion mutant mtDNA (DeltamtDNA) were generated by introduction of the DeltamtDNA from cultured cells into fertilized eggs of C57BL/6J (B6) strain mice. Great advantages of mito-mice are that they share exactly the same nuclear-genome background, and that their genetic variations are restricted to proportions of pathogenic DeltamtDNA. Since accumulation of DeltamtDNA to more than 75% induced respiration defects, the disease phenotypes observed exclusively in mito-mice carrying more than 75% DeltamtDNA should be due to accumulated DeltamtDNA. In this study, we focused on the expressions of hearing loss and diabetic phenotypes, since these common age-associated abnormalities have sometimes been reported to be inherited maternally and to be associated with pathogenic mutant mtDNAs. The results showed that accumulation of exogenously introduced DeltamtDNA was responsible for hearing loss, but not for expression of diabetic phenotypes in mito-mice. Copyright 2004 Elsevier Inc.