MOUSE GENETICS IN THE 21ST-CENTURY - USING GENE TARGETING TO CREATE ACORNUCOPIA OF MOUSE MUTANTS POSSESSING PRECISE GENETIC MODIFICATIONS

Over 1500 mouse mutants have been identified, but few of the genes res ponsible for the defects have been identified. Recent developments in the area of gene targeting are revolutionizing the field of mouse gene tics and our understanding of numerous genes, including those thought to be involved in cell proliferation and differentiation. Gene targeti ng was developed as a method for producing a predetermined mutation in a specific endogenous gene. Advances in the design of targeting vecto rs and in the use of embryonic stem cells have permitted the productio n of numerous mutant mice with null mutations in specific genes. These mutant mice will be critical for investigating the in vivo functions of many genes that have been cloned in recent years. This review discu sses a wide range of new developments in the field of gene targeting w ith a focus on issues to be considered by those planning to use this n ew technology. It also examines some of the lessons learned from recen t gene targeting studies and discusses different applications of the t echnology that are likely to generate scores of new animal models for a wide range of human diseases.