Genetically modified mice in neuropharmacology

Since the first transgenic mouse was reported in 1980, genetically engineer ed mice have become an invaluable biological tool for better understanding of physiological and pathological processes in many fields of biomedical re search. The transgenic technology allows researchers to carry out specific genetic manipulation in all cells of a laboratory animal, and makes it poss ible to dissect gene function in a living organism. In the field of neurosc iences these animals have contributed greatly to shed light on basic mechan isms of brain function as well as to generate useful animal models for stud ying human neurological disorders. In this review, the different techniques available for generating specific mutations in the mouse genome will be de scribed, from pronuclear microinjection to gene targeting in embryonic stem cells, and to the second generation of inducible and conditional knockout mice. Then, the impact of transgenic mouse models as an alternative or addi tional approach to neuropharmacology will be discussed, not only for the st udy of molecular mechanisms in the central nervous system but also for the identification of new biological targets for innovative pharmacological the rapy. (C) 1999 Academic Press.