A Human Hepatocyte-Bearing Mouse: An Animal Model to Predict Drug Metabolism and Effectiveness in Humans

Abstract

Preclinical studies to predict the efficacy and safety of drugs have conventionally been conducted almost exclusively in mice and rats as rodents, despite the differences in drug metabolism between humans and rodents. Furthermore, human (ℎ) viruses such as hepatitis viruses do not infect the rodent liver. A mouse bearing a liver in which the hepatocytes have been largely repopulated with ℎ-hepatocytes would overcome some of these disadvantages. We have established a practical, efficient, and large-scale production system for such mice. Accumulated evidence has demonstrated that these hepatocyte-humanized mice are a useful and reliable animal model, exhibiting ℎ-type responses in a series of in vivo drug processing (adsorption, distribution, metabolism, excretion) experiments and in the infection and propagation of hepatic viruses. In this review, we present the current status of studies on chimeric mice and describe their usefulness in the study of peroxisome proliferator-activated receptors.