The variability of the harlequin mouse phenotype resembles that of human mitochondrial-complex I-deficiency syndromes

PLoS One. 2008 Sep 15;3(9):e3208. doi: 10.1371/journal.pone.0003208.


Background: Despite the considerable progress made in understanding the molecular bases of mitochondrial diseases, no effective treatments have been developed to date. Faithful animal models would be extremely helpful for designing such treatments. We showed previously that the Harlequin mouse phenotype was due to a specific mitochondrial complex I deficiency resulting from the loss of the Apoptosis Inducing Factor (Aif) protein.

Methodology/principal findings: Here, we conducted a detailed evaluation of the Harlequin mouse phenotype, including the biochemical abnormalities in various tissues. We observed highly variable disease expression considering both severity and time course progression. In each tissue, abnormalities correlated with the residual amount of the respiratory chain complex I 20 kDa subunit, rather than with residual Aif protein. Antioxidant enzyme activities were normal except in skeletal muscle, where they were moderately elevated.

Conclusions/significance: Thus, the Harlequin mouse phenotype appears to result from mitochondrial respiratory chain complex I deficiency. Its features resemble those of human complex I deficiency syndromes. The Harlequin mouse holds promise as a model for developing treatments for complex I deficiency syndromes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Brain / metabolism
  • Electron Transport Complex I / deficiency*
  • Electron Transport Complex I / genetics*
  • Female
  • Genotype
  • Humans
  • Male
  • Mice
  • Mitochondria
  • Models, Genetic
  • Phenotype
  • Reproducibility of Results
  • Superoxide Dismutase / metabolism
  • Time Factors


  • Antioxidants
  • Superoxide Dismutase
  • Electron Transport Complex I