| First Author | Dell'agnello C | Year | 2007 |
| Journal | Hum Mol Genet | Volume | 16 |
| Issue | 4 | Pages | 431-44 |
| PubMed ID | 17210671 | Mgi Jnum | J:117871 |
| Mgi Id | MGI:3697938 | Doi | 10.1093/hmg/ddl477 |
| Citation | Dell'agnello C, et al. (2007) Increased longevity and refractoriness to Ca2+-dependent neurodegeneration in Surf1 knockout mice. Hum Mol Genet 16(4):431-44 |
| abstractText | Leigh syndrome associated with cytochrome c oxidase (COX) deficiency is a mitochondrial disorder usually caused by mutations of SURF1, a gene encoding a putative COX assembly factor. We present here a Surf1-/- recombinant mouse obtained by inserting a loxP sequence in the open reading frame of the gene. The frequency of -/-, +/+ and +/- genotypes in newborn mice followed a mendelian distribution, indicating that the ablation of Surf1 is compatible with postnatal survival. The biochemical and assembly COX defect was present in Surf1(loxP)-/- mice, but milder than in humans. Surprisingly, not only these animals failed to show spontaneous neurodegeneration at any age, but they also displayed markedly prolonged lifespan, and complete protection from Ca(2+)-dependent neurotoxicity induced by kainic acid. Experiments on primary neuronal cultures showed markedly reduced rise of cytosolic and mitochondrial Ca(2+) in Surf1(loxP)-/- neurons, and reduced mortality, compared to controls. The mitochondrial membrane potential was unchanged in KO versus wild-type neurons, suggesting that the effects of the ablation of Surf1 on Ca(2+) homeostasis, and possibly on longevity, may be independent, at least in part, from those on COX assembly and mitochondrial bioenergetics. |
