A conditional mouse model of complex II deficiency manifesting as Leigh-like syndrome

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.

Keywords: familial paraganglioma; hypoxia; mitochondrial disease; succinate dehydrogenase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Blotting, Western
  • Body Composition / genetics
  • Body Composition / physiology
  • Disease Models, Animal
  • Female
  • Hypoxia / genetics
  • Hypoxia / metabolism
  • Male
  • Mice
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / metabolism*
  • Paraganglioma / genetics
  • Paraganglioma / metabolism
  • Succinate Dehydrogenase / genetics
  • Succinate Dehydrogenase / metabolism


  • Succinate Dehydrogenase