Abstract

Publisher Summary This chapter discusses the construction and analysis of multidrug resistance transgenic mice. It discusses the generation of transgenic mice expressing human MDR1 from two transgenes in hematopoietic cells. Transgenic mice derived by pronuclear injection have proven to be a useful tool for in vivo study of multidrug resistance (MDR) mediated by the MDR1 gene product—human P-glycoprotein (HPgp). It is desirable to use animal models to measure the antitumor effects of MDR drug dose escalation and in the long term, to evaluate anticancer therapies directed against multidrug-resistant tumors of various histology. Transgenic mouse models in which HPgp is expressed in blood cells have the advantages of well-defined ectopic expression at physiologic levels, a single mechanism of drug resistance, convenient and rapid assays, and simple determination of reversing agent selectivity—that is, preferential chemosensitization in HPgp-positive cells.

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