title: Genetic background influences mitochondrial function: modeling mitochondrial disease for therapeutic development.
abstract: Genetic background strongly influences the phenotype of human mitochondrial diseases. Mitochondrial biogenesis and function require up to 1500 nuclear genes, providing myriad opportunities for effects on disease expression. Phenotypic variability, combined with relative rarity, constitutes a major obstacle to establish cohorts for clinical trials. Animal models are, therefore, potentially valuable. However, several of these show no or very mild disease phenotypes compared with patients and can not be used for therapeutic studies. One reason might be the insufficient attention paid to the need for genetic diversity in order to capture the effects of genetic background on disease expression. Here, we use data from various models to emphasize the need to preserve genetic diversity when studying mitochondrial disease phenotypes or drug effects.
authors.affiliation: Inserm, U676, Paris, 75019, France.
authors.forename: Paule
authors.initials: P
authors.lastname: Bénit
authors.forename: Riyad
authors.initials: R
authors.lastname: El-Khoury
authors.forename: Manuel
authors.initials: M
authors.lastname: Schiff
authors.forename: Annie
authors.initials: A
authors.lastname: Sainsard-Chanet
authors.forename: Pierre
authors.initials: P
authors.lastname: Rustin
mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000473:pathology; D028361:Mitochondrial Diseases / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial