Study of the role of hydrogen peroxide in physiopathology using a novel transgenic mouse model overexpressing the H2O2-generating complex DUOX/DUOXA

Supervisor: Dr. Xavier De Deken

Accumulating evidence suggests that sustained hydrogen peroxide production could be mutagenic promoting benign or malignant tumors, or involved in inflammatory diseases. However, until now there is no evidence of such effects mediated by H2O2 in an in vivo model. In the present project, we propose to clarify these in vitro observations by creating and analyzing a new animal model overexpressing the H2O2 generator DUOX/DUOXA complex. Transgenic mice will combine the conditional Cre/LoxP and the inducible Tet-On systems targeted into the ROSA26 locus. After mating with available tissue specific Cre-expressing mice, pathological consequences of chronic H2O2 exposure will be studied at multiple cellular and molecular levels upon doxycycline treatments (histopathology of tissue lesions, gene profiling of oxidative stress responses). Oxidative stress-induced diseases will be promoted by treatments with selenium-deficient diets, inhibitor of antioxidant systems (GPX) or by crossbreeding with ROS-defense deficient mice. To favor carcinogenesis, transgenic animals could be mate with other existing mouse models of cancers or p53KO mice.

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