3] Use of gene knockout mice to establish lipase function

Abstract

This chapter discusses the use of gene knockout technology to generate transgenic mice with defective expression of specific lipase genes and the use of these animals to address the physiologic function of these proteins. The utilities for production of gene knockout mice are manifold. First, gene knockout mice can be produced as an animal model for human diseases. A second utility for the production of knockout mice is to explore the physiologic function and significance of specific genes. One approach to address the physiologic function of the pancreatic carboxyl ester lipase (CEL) is to produce animals defective in expression of the CEL gene. Production of CEL gene knockout mice was accomplished by homologous recombination of an exogenously added disrupted CEL gene with the endogenous CEL gene in mouse embryonic stem (ES) cells. The CEL gene targeted ES cells were then used to produce a mouse model with defective CEL gene expression. These animals are useful for determining the significance of the cholesterol esterase in lipid metabolism, including its function in dietary fat and cholesterol absorption.