Gene therapy for progeny of mito-mice carrying pathogenic mtDNA by nuclear transplantation.
Pathogenic mutations in mtDNAs have been shown to be responsible for expression of respiration defects and resultant expression of mitochondrial diseases. This study directly addressed the issue of gene therapy of mitochondrial diseases by using nuclear transplantation of zygotes of transmitochondria mice (mito-mice). Mito-mice expressed respiration defects and mitochondrial diseases due to accumulation of mtDNA carrying a large-scale deletion (DeltamtDNA). Second polar bodies were used as biopsy samples for diagnosis of mtDNA genotypes of mito-mouse zygotes. Nuclear transplantation was carried out from mito-mouse zygotes to enucleated normal zygotes and was shown to rescue all of the F(0) progeny from expression of respiration defects throughout their lives. This procedure should be applicable to patients with mitochondrial diseases for preventing their children from developing the diseases.
Sato
Akitsugu
A
Graduate School of Life and Environmental Sciences, Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8572, Japan.
Kono
Tomohiro
T
Nakada
Kazuto
K
Ishikawa
Kaori
K
Inoue
Shin-Ichi
S
Yonekawa
Hiromichi
H
Hayashi
Jun-Ichi
J
D000375:Aging / Q000235:genetics; D000818:Animals; D015139:Blotting, Southern; D004272:DNA, Mitochondrial / Q000235:genetics*; D047109:Fetal Development; D015316:Genetic Therapy; D005838:Genotype; D006128:Growth / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D053652:Nuclear Transfer Techniques; D010101:Oxygen Consumption; D010641:Phenotype
D004272:DNA, Mitochondrial