The invention provides non-human transgenic animals, and cell lines, host cells, tissues and isolated organs, comprising the human UDP-glucuronosyltransferase IA (UGT1A) gene locus. In one aspect, the endogenous UGT1A gene locus of the non-human transgenic animal has been partially or completely "knocked out." In another aspect, the invention is directed to drug screening, design and discovery. In another aspect, the invention is directed to determining the toxicity or metabolism of a compound, e.g., a toxin or drug, including environmental, dietary, cosmetic, biological warfare or other known or potentially toxic compounds. In another aspect, the invention is directed to deteuiining the toxicity or metabolism of a compound during a particular metabolic state of an animal, e.g., including pregnancy, stress, diet, age or a particular genotype.