| First Author | Peralta S | Year | 2014 |
| Journal | Hum Mol Genet | Volume | 23 |
| Issue | 6 | Pages | 1399-412 |
| PubMed ID | 24154540 | Mgi Jnum | J:206222 |
| Mgi Id | MGI:5548237 | Doi | 10.1093/hmg/ddt526 |
| Citation | Peralta S, et al. (2014) Partial complex I deficiency due to the CNS conditional ablation of Ndufa5 results in a mild chronic encephalopathy but no increase in oxidative damage. Hum Mol Genet 23(6):1399-412 |
| abstractText | Deficiencies in the complex I (CI; NADH-ubiquinone oxidoreductase) of the respiratory chain are frequent causes of mitochondrial diseases and have been associated with other neurodegenerative disorders, such as Parkinson's disease. The NADH-ubiquinone oxidoreductase 1 alpha subcomplex subunit 5 (NDUFA5) is a nuclear-encoded structural subunit of CI, located in the peripheral arm. We inactivated Ndufa5 in mice by the gene-trap methodology and found that this protein is required for embryonic survival. Therefore, we have created a conditional Ndufa5 knockout (KO) allele by introducing a rescuing Ndufa5 cDNA transgene flanked by loxP sites, which was selectively ablated in neurons by the CaMKIIalpha-Cre. At the age of 11 months, mice with a central nervous system knockout of Ndufa5 (Ndufa5 CNS-KO) showed lethargy and loss of motor skills. In these mice cortices, the levels of NDUFA5 protein were reduced to 25% of controls. Fully assembled CI levels were also greatly reduced in cortex and CI activity in homogenates was reduced to 60% of controls. Despite the biochemical phenotype, no oxidative damage, neuronal death or gliosis were detected in the Ndufa5 CNS-KO brain at this age. These results showed that a partial defect in CI in neurons can lead to late-onset motor phenotypes without neuronal loss or oxidative damage. |
