Transgenic Analysis of Human Drug–Metabolizing Enzymes: Preclinical Drug Development and Toxicology

Table 1.

Use of Transgenic Animals

System	Potential Use
Gene inactivation or deletion (“knockout”)	• Characterization of endogenous function(s) of gene product
	• Role of gene product in stress response, toxicity and carcinogenesis
	• Development of disease models
Insertion of transgene	• Characterization of function(s) of transgene product
	• Role of transgene in activation or detoxification of xenobiotics
	• Development of disease models
Promoter–Reporter (lacZ , GFP, luciferase)	• Characterization of promotor regulation
	• Definition of gene expression pattern
	• Toxicity screens
Promoter–Transgene	• Defined spatiotemporal control of transgene expression
	• Role in pharmacokinetics and toxic response
Gene replacement (“humanization”)
	• Characterization of function(s) of human gene product
	• Role of polymorphic alleles in toxicity and carcinogenesis