Application of ES cells for generation of respiration-deficient mice carrying mtDNA with a large-scale deletion.

ABSTRACT

In a previous study, we used mouse zygotes as recipients of mtDNA with a large-scale deletion mutation (DeltamtDNA) and generated respiration-deficient mice (mito-mice) carrying DeltamtDNA. In this study, we used mouse ES cells as recipients of DeltamtDNA, and generated mito-mice with DeltamtDNA only when the ES cells carried 17% DeltamtDNA. No chimera mice or their F(1) progenies were obtained from ES cells carrying more than 61% DeltamtDNA. These observations suggest that respiratory defects of ES cells inhibit their normal differentiation into chimera mice and mito-mice, and that ES cells are more effective than zygotes for generation of mito-mice carrying mtDNAs without significant pathogenic mutations.