The present invention relates to non-human transgenic animals, tissues and/or cells derived therefrom having depleted or ablated cytochrome P450 reductase (CPR) expression, methods of producing such animals, tissues and/or cells, and methods of using such animals, tissues and/or cells. Non-human transgenic animals, tissues and or cells derived therefrom of the present invention may be used for, but non exclusively, in both in vivo and in vitro screening of therapeutic agents, drug development, drug metabolism/disposition studies and studying disease states, pregnancy, fetal development, modulation of hormone function and hormone levels, and other pathways and/or substrate metabolism in which cytochrome P450 plays a role.