title: Generation of Xenomitochondrial Embryonic Stem Cells for the Production of Live Xenomitochondrial Mice.
abstract: The unique features of the mitochondrial genome, such as its high copy number and lack of defined mechanisms of recombination, have hampered efforts to manipulate its sequence to create specific mutations in mouse mtDNA. As such, the generation of in vivo mouse models of mtDNA disease has proved technically challenging. This chapter describes a unique approach to create mitochondrial oxidative phosphorylation (OXPHOS) defects in mouse ES cells by transferring mtDNA from different murid species into Mus musculus domesticus ES cells using cytoplasmic hybrid ("cybrid") fusion. The resulting "xenocybrid" ES cells carry OXPHOS defects of varying severity, and can be utilized to generate live mouse models of mtDNA disease.
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, 32 Gisborne Street, East Melbourne, VIC, 3002, Australia.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Trounce
authors.affiliation: Centre for Genetic Diseases, Hudson Institute of Medical Research, Clayton, VIC, 3168, Australia.
authors.forename: Jessica
authors.initials: J
authors.lastname: Ackerley
authors.affiliation: Centre for Genetic Diseases, Hudson Institute of Medical Research, Clayton, Melbourne, VIC, Australia. matthew.mckenzie@hudson.org.au.
authors.forename: Matthew
authors.initials: M
authors.lastname: McKenzie
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology; D002459:Cell Fusion / Q000379:methods*; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000502:physiology; D002678:Chimera / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D007739:L Cells / Q000166:cytology; D051379:Mice; D008928:Mitochondria / Q000235:genetics*; D028361:Mitochondrial Diseases / Q000235:genetics; D053652:Nuclear Transfer Techniques; D021141:Nucleic Acid Amplification Techniques; D010085:Oxidative Phosphorylation
chemical_list: D004272:DNA, Mitochondrial
keywords: Embryonic stem cell s; Fibroblasts; Fusion; Mouse; Xenocybrid