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

2004; Elsevier BV; Volume: 323; Issue: 1 Linguagem: Inglês

10.1016/j.bbrc.2004.08.073

1090-2104

Kazuto Nakada, Akitsugu Sato, Hirohito Sone, Atsuko Kasahara, Katsuhisa Ikeda, Yasuo Kagawa, Hiromichi Yonekawa, Jun‐Ichi Hayashi,

ATP Synthase and ATPases Research

Mito-mice carrying various proportions of deletion mutant mtDNA (ΔmtDNA) were generated by introduction of the ΔmtDNA 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 ΔmtDNA. Since accumulation of ΔmtDNA to more than 75% induced respiration defects, the disease phenotypes observed exclusively in mito-mice carrying more than 75% ΔmtDNA should be due to accumulated ΔmtDNA. 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 ΔmtDNA was responsible for hearing loss, but not for expression of diabetic phenotypes in mito-mice.