Abstract: This invention provides a system for rapid determination of pharmacologic effects on target tissue types in cell populations cultured in vitro. The cells contain a promoter-reporter construct that reflects a toxicologic or metabolic change caused by the agent being screened. The promoter is taken from a gene known to be up- or down-regulated according to the metabolic state of the cell, and linked to a reporter gene that provides an external signal for monitoring promoter activity. The promoter-reporter cells may be produced by placing these genetic alterations into a line of human embryonic stem cells, bulking up the cells to any extent desired, and then differentiating the cells into the desired tissue type. This disclosure explains some of the powerful features of the promoter-reporter cells of this invention, and shows various ways the skilled reader can use the invention for pharmaceutical development and testing, or to monitor graft survival.

Abstract: 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.