Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA.
GEMpath, Longmont, Colorado, USA.
FASEB J. 2019 Dec;33(12):13189-13201. doi: 10.1096/fj.201802655RR. Epub 2019 Aug 30.
Leigh syndrome embodies degenerative disorders with a collection of symptoms secondary to inborn errors of metabolism. Combinations of hypomorphic and loss-of-function alleles in many genes have been shown to result in Leigh syndrome. Interestingly, deficiency for the tricarboxylic acid cycle enzyme succinate dehydrogenase (SDH) can lead to Leigh-like syndrome in some circumstances and to cancer (paraganglioma, renal cell carcinoma, gastrointestinal stromal tumor) in others. In our experiments originally intended to create an inducible whole-body SDH-loss mouse model of tumorigenesis, we generated a condition reminiscent of Leigh-like syndrome that is lethal to mice within 4 wk. Remarkably, as has been shown for other mitochondrial diseases, chronic hypoxia offers substantial protection to mice from this condition after systemic SDH loss, allowing survival in the context of profoundly impaired oxidative metabolism.-Al Khazal, F., Holte, M. N., Bolon, B., White, T. A., LeBrasseur, N., Maher, L. J. III. A conditional mouse model of complex II deficiency manifesting as Leigh-like syndrome.
Leigh 综合征是一种退行性疾病，其一系列症状继发于先天性代谢错误。许多基因中的低功能和功能丧失等位基因的组合已被证明可导致 Leigh 综合征。有趣的是，三羧酸循环酶琥珀酸脱氢酶 (SDH) 的缺乏在某些情况下可导致 Leigh 样综合征，而在其他情况下可导致癌症（副神经节瘤、肾细胞癌、胃肠道间质瘤）。在我们最初旨在创建诱导型全身 SDH 缺失肿瘤发生小鼠模型的实验中，我们产生了一种类似于 Leigh 样综合征的情况，该综合征在 4 周内可使小鼠致死。值得注意的是，正如其他线粒体疾病所表明的那样，慢性缺氧为全身性 SDH 缺失后的小鼠提供了对这种情况的实质性保护，允许在氧化代谢严重受损的情况下存活。-Al Khazal，F.，Holte，M. N.，Bolon，B.，White，T. A.，LeBrasseur，N.，Maher，L. J. III. 表现为 Leigh 样综合征的复合物 II 缺陷的条件性小鼠模型。
