Mutant mouse models of oxidative stress.
Oxidative stress corresponds to an excess in reactive oxygen species (ROS) including free radicals which are highly reactive with cellular constituents. Thereby ROS induce damage to DNA, proteins and lipids, which are all involved in the etiology of numerous pathologies such as cancer. To prevent potential damage, a tight regulation of ROS level is achieved through numerous enzyme systems and small molecules such as glutathione and vitamin C. Mutant mouse models targeting antioxidant enzymes have confirmed their essential role in ROS level control, and have shown a limited redundancy of their activity. Additionally, a number of other mutant mouse models exhibit increased ROS levels, suggesting an antioxidant role for the corresponding targeted gene. This is the case for mice deficient for the transcription factors p53, JunD, FoxOs, and HIF-2alpha, which are involved in the modulation of antioxidant enzymes expression. Mice deficient either for the stress factor TP53INP1, which is a target of p53, or for ATM involved in DNA damage sensoring, also show a constitutive oxidative stress. Finally, the last reported case of mice with a permanent oxidative stress targets Bmi which is a transcriptional repressor of the polycomb family. Interestingly, most of these "oxidative stressed mice" either spontaneously develop cancers or are more susceptible than wild-type to tumor-induced protocols. Altogether, these models markedly reinforce the causal link between oxidative stress and cancer. In the future, they will be helpful tools for basic research aimed at unraveling the interplay between redox control actors as well as their relative importance. In addition, these oxidative stressed mouse models may be useful for applied research in particular in preclinical assays where redox status regulation is absolutely required.
Pouyet
Laurent
L
INSERM U624, Case 915 Parc Scientifique de Luminy, 13288 Marseille Cedex 9, France.
Carrier
Alice
A
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009369:Neoplasms / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics
D000975:Antioxidants; D017382:Reactive Oxygen Species; D014157:Transcription Factors