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

Fatimah Al Khazal, Molly Nelson Holte, Brad Bolon, Thomas A. White, Nathan LeBrasseur, L. James Maher

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)13189-13201
Number of pages13
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume33
Issue number12
DOIs
StatePublished - Dec 1 2019

Fingerprint

Leigh Disease
Succinate Dehydrogenase
Metabolism
Tumors
Inborn Errors Metabolism
Genes
Mitochondrial Diseases
Paraganglioma
Cells
Gastrointestinal Stromal Tumors
Citric Acid Cycle
Renal Cell Carcinoma
Enzymes
Carcinogenesis
Alleles
Experiments
Neoplasms

Keywords

  • familial paraganglioma
  • hypoxia
  • mitochondrial disease
  • succinate dehydrogenase

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

A conditional mouse model of complex II deficiency manifesting as Leigh-like syndrome. / Al Khazal, Fatimah; Holte, Molly Nelson; Bolon, Brad; White, Thomas A.; LeBrasseur, Nathan; Maher, L. James.

In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 33, No. 12, 01.12.2019, p. 13189-13201.

Research output: Contribution to journalArticle

Al Khazal, Fatimah ; Holte, Molly Nelson ; Bolon, Brad ; White, Thomas A. ; LeBrasseur, Nathan ; Maher, L. James. / A conditional mouse model of complex II deficiency manifesting as Leigh-like syndrome. In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019 ; Vol. 33, No. 12. pp. 13189-13201.
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