Mito-mice: animal models for mitochondrial DNA-based diseases.
We have successfully produced "Mito-mice" harbouring a pathogenic mtDNA mutation. We generated the mice by introducing mitochondria with a 4696 base-pair mtDNA deletion (Delta mtDNA4696) into mouse embryos. This deletion encompasses nucleotides 7759-12 454 and includes six tRNA genes and seven structural genes. In Mito-mice, the Delta mtDNA4696 is transmitted maternally, and induces mitochondrial dysfunction in various tissues. Most of the Mito-mice with high proportions of the Delta mtDNA4696 died at about age 6 months due to renal failure. Mito-mice are the first animal model for mtDNA-based diseases and will be valuable for studying pathogenesis and for identifying effective drug and gene therapies.
Nakada
K
K
Institute of Biological Sciences, University of Tsukuba, Ibaraki 305-8572, Japan
Inoue
K
K
Hayashi
J I
JI
D000818:Animals; D002678:Chimera; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology; D023421:Models, Animal; D015053:Zygote / Q000378:metabolism
D004272:DNA, Mitochondrial