title: Mouse models of mitochondrial DNA defects and their relevance for human disease.
abstract: Qualitative and quantitative changes in mitochondrial DNA (mtDNA) have been shown to be common causes of inherited neurodegenerative and muscular diseases, and have also been implicated in ageing. These diseases can be caused by primary mtDNA mutations, or by defects in nuclear-encoded mtDNA maintenance proteins that cause secondary mtDNA mutagenesis or instability. Furthermore, it has been proposed that mtDNA copy number affects cellular tolerance to environmental stress. However, the mechanisms that regulate mtDNA copy number and the tissue-specific consequences of mtDNA mutations are largely unknown. As post-mitotic tissues differ greatly from proliferating cultured cells in their need for mtDNA maintenance, and as most mitochondrial diseases affect post-mitotic cell types, the mouse is an important model in which to study mtDNA defects. Here, we review recently developed mouse models, and their contribution to our knowledge of mtDNA maintenance and its role in disease.
authors.affiliation: Biomedicum Helsinki, Research Programme of Molecular Neurology, r.C523B, University of Helsinki, Haartmaninkatu 8, PO Box 63, 00290 Helsinki, Finland. henna.tyynismaa@helsinki.fi
authors.forename: Henna
authors.initials: H
authors.lastname: Tyynismaa
authors.forename: Anu
authors.initials: A
authors.lastname: Suomalainen
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D004265:DNA Helicases / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D018628:Gene Dosage; D050259:Genes, Mitochondrial; D005818:Genetic Engineering / Q000379:methods; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains / Q000235:genetics*; D008822:Mice, Transgenic; D028361:Mitochondrial Diseases / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D012264:Ribonucleotide Reductases / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D013937:Thymidine Kinase / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D012264:Ribonucleotide Reductases; C486561:Rrm2b protein, mouse; C105339:thymidine kinase 2; D013937:Thymidine Kinase; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human; C498803:Polg protein, mouse; C513299:Twnk protein, mouse; D004265:DNA Helicases; C431576:TWNK protein, human