Table IV.

Mouse models carrying mutations in the mtDNA

Gene	Mitochondrial Function	Genetic Manipulation	Phenotype	References
“Common deletion”	Encompasses tRNAs and 7 structural genes of CI, CIV, CV	Electrofusion of pronucleus- stage embryos with several enucleated cytoplasts of the ΔmtDNA cybrids. Positive clones were transferred to the oviduct of pseudo pregnant females	Mosaic pattern of COX negative and positive fibers both in heart and muscle; peaks of lactic acid in peripheral blood; kidney impairment	(Inoue, 2000)
Cox1	Catalytic subunit of CIV	Fusion of cytoplasts carrying the homoplasmic T6589C missense mutation with ES cells deprived of mtDNA. Positive clones were introduced into 8-cell-stage embryos	Growth retardation and CIV deficiency in brain, heart, liver and skeletal muscles. No motor or neurological phenotype	(Kasahara, 2006)
Cox1/Nd6	Catalytic subunits of CIV and CI	Fusion of cytoplasts carrying both the homoplasmic T6589C missense mutation and a Nd6 frameshift mutation with ES cells devoid of mitochondria (ρ0)	Mitochondrial myopathy and cardiomyopathy; decrease CIV activity in brain, liver, heart and skeletal muscle; RRF and abnormal mitochondria in muscle. No motor or neurological phenotype	(Fan, 2008)
Nd6	Core subunit of CI	Cells containing the homoplasmic G13997A missense mutation were fused with ρo ES cells. Positive clones were fused with a 8- cell-stage embryos and implanted into pseudo pregnant female	CI+III in different tissues. Age associated disorders at longer observation	(Hashizume , 2012)
		Enucleated LMTK cell lines carrying homoplasmic G13997A mutation were fused with female mouse ES cells deprived of mitochondria. Positive clones were injected into blastocyst to produce chimera females	Phenotype resembling the clinical features of LHON patients, characterized by decreased retinal response and swollen axons in the optic tract; CI deficiency in liver and brain; high levels of ROS in the brain.	(Lin, 2012)
tRNALys	Mitochondrial translational component	The somatic G7731A mutation was introduced in female ES cells lacking mitochondria. Mice with different loads of G7731A mtDNA were obtained in subsequent generations.	Transmitochondrial mice carrying 85% tRNALys G8344A displayed short body length, muscle weakness and RRF. Respiratory chain defect and ROS production was particularly evident in skeletal muscle.	(Shimizu, 2014)