Table I.
Mouse models of Complex I deficiency
| Gene | Mitochondrial function |
Genetic Manipulation | Phenotype | References |
|---|---|---|---|---|
| Ndufs4 | Assembly/stability of CI |
Knockout: -Whole body (Mox2-Cre) |
Leigh-like, blindness, ataxia, retarded growth rate, lethargy |
(Kruse, 2008) |
| Knockout: -Whole body (transposable element) |
Neurological impairment |
(Leong, 2012) | ||
| Conditional knockout: -Neurons and glia (Nestin-Cre and local injection of AAV Cre) |
Fatal progressive encephalopathy, ataxia, glial reactivity and neuronal loss; breathing dysfunction |
(Quintana, 2010; Quintana, 2012) |
||
| -Dopaminergic neurons (Dat-Cre) |
No overt neurodegeneration |
(Sterky, 2012) | ||
| -Heart/skeletal-muscle (Mck-Cre) |
Cardiomyopathy | (Sterky, 2012) | ||
| -Heart (αMhc-Cre) | Cardiomyopathy induced after stress condition |
(Karamanlidis, 2013) | ||
| Knock-in: (Stop codon) |
Embryonic lethality | (Ingraham, 2009) | ||
| Ndufs6 | Involved in the activity of CI |
Knock-down: -whole body (gene trap) |
Cardiomyopathy, systolic dysfunction |
(Ke, 2012) |
| Renal disease, with altered ultrastructure and release of kidney damage biomarkers in urine |
(Forbes, 2013) | |||
| Ndufa5 | Unknown function (accessory subunit that is inserted at a late stage in the assembly process of CI) |
Knockout: -Whole body (gene trap) |
Embryonic lethality | (Peralta, 2013) |
| Conditional knockout: - Neurons (CaMKIIα-Cre) |
Partial defect of CI in neurons that leads to lethargy and loss of motor skills at 10 months. |
(Peralta, 2013) |