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


RESULTS
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
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.
Bénit
Paule
P
Inserm, U676, Hôpital Robert Debré, Paris, France.
Goncalves
Sergio
S
Dassa
Emmanuel Philippe
EP
Brière
Jean-Jacques
JJ
Rustin
Pierre
P
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D042967:Electron Transport Complex I / Q000172:deficiency* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D008928:Mitochondria; D008957:Models, Genetic; D010641:Phenotype; D015203:Reproducibility of Results; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D000975:Antioxidants; D013482:Superoxide Dismutase; D042967:Electron Transport Complex I
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