title: Assaying the probabilities of obtaining maternally inherited heteroplasmy as the basis for modeling OXPHOS diseases in animals.
abstract: Gross alterations in cell energy metabolism underlie manifestations of hereditary OXPHOS (oxidative phosphorylation) diseases, many of which depend on proportion of mutant mitochondrial DNA (mtDNA) in tissues. An animal model of OXPHOS disease with maternal inheritance of mitochondrial heteroplasmy might help understanding the peculiarities of abnormal mtDNA distribution and its effect on pre- and postnatal development. Previously we obtained mice that carry human mtDNA in some tissues. It co-existed with murine mtDNA (heteroplasmy) and was transmitted maternally to the progeny of animals developed from zygotes injected with human mitochondria. To analyze the probability of obtaining heteroplasmic mice we increased the number of experiments with early embryos and obtained more specimens from F1. About 33% of zygotes injected with human mtDNA developed into post-implantation embryos (7th-13th days). Lower amount of such developed into neonate mice (ca. 21%). Among post-implantation embryos and in generations F0 and F1 percentages of human mtDNA-carriers were ca. 14-16%. Such percentages are sufficient for modeling maternally inherited heteroplasmy in small animal groups. More data are needed to understand the regularities of anomalous mtDNA distribution among cells and tissues and whether heart and muscles frequently carrying human mtDNA in our experiments are particularly susceptible to heteroplasmy.
authors.affiliation: Department of Molecular Genetics, Institute of Experimental Medicine, 12 Pavlov Street, Saint-Petersburg 197376, Russia.
authors.forename: Mikhail G
authors.initials: MG
authors.lastname: Bass
authors.forename: Vassilina A
authors.initials: VA
authors.lastname: Sokolova
authors.forename: Maria E
authors.initials: ME
authors.lastname: Kustova
authors.forename: Elena V
authors.initials: EV
authors.lastname: Grachyova
authors.forename: Oksana V
authors.initials: OV
authors.lastname: Kidgotko
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Sorokin
authors.forename: Vadim B
authors.initials: VB
authors.lastname: Vasilyev
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000502:physiology; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000502:physiology; D050259:Genes, Mitochondrial; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000235:genetics* / Q000502:physiology / Q000637:transplantation; D028361:Mitochondrial Diseases / Q000235:genetics*; D009928:Organ Specificity; D010085:Oxidative Phosphorylation; D011336:Probability; D015053:Zygote / Q000502:physiology
chemical_list: D004272:DNA, Mitochondrial