Application of disease-model mice with mutant mtDNA for precise investigation of its pathogenesis

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Purpose 1 : Precise investigation of pathogenesis.Results : We provided first evidence that the mutated mtDNA is responsible for male infertility, which had been published in PNAS 103 : 15148-15153, 2006.Purpose 2 : Transmission profiles of the mtDNA to following generations.Results : It has been controversial of whether there is recombination in mammalian mtDNA. Our study provided convincing evidence that mouse mtDNA rarely recombine each other by creating mice carrying heteroplasmic mtDNAs, which had been published in PNAS 102 : 6057-6062, 2005. Moreover, we showed that the mitochondrial bottleneck is not generated due to a mtDNA copy number drastic decline in early oogenesis rather to a small effective number of segregation units for mtDNA in mouse germ cells, which had been published in Nature Genet. 39 : 386-390, 2007.Purpose 3 : Development of gene therapy for mito-mice expressing respirtion defects.Results : We can provide the first report of the success of gene therapy by application of nuclear transplantation technique to firtilized eggs of mito-mice, which had been published in PNAS 102 : 16765-16770, 2005.