NDUFS4: creation of a mouse model mimicking a Complex I disorder

Mitochondrion. 2009 Jun;9(3):204-10. doi: 10.1016/j.mito.2009.02.001. Epub 2009 Feb 11.

Abstract

The Complex I NADH dehydrogenase-ubiquinone-FeS 4 (NDUFS4) subunit gene is involved in proper Complex I function such that the loss of NDUFS4 decreases Complex I activity resulting in mitochondrial disease. Therefore, a mouse model harboring a point mutation in the NDUFS4 gene was created. An embryonic lethal phenotype was observed in homozygous (NDUFS4(-/-)) mutant fetuses. Mitochondrial function was impaired in heterozygous animals based on oxygen consumption, and Complex I activity in NDUFS4 mouse mitochondria. Decreased Complex I activity with unaltered Complex II activity, along with an accumulation of lactate, were consistent with Complex I disorders in this mouse model.

Publication types

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

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Electron Transport Complex I / deficiency*
  • Electron Transport Complex I / genetics
  • Female
  • Heterozygote
  • Homozygote
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / pathology*
  • Point Mutation*

Substances

  • Ndufs4 protein, mouse
  • Electron Transport Complex I