Genetically modified mice in neuropharmacology

Since the first transgenic mouse was reported in 1980, genetically engineered mice have become an invaluable biological tool for better understanding of physiological and pathological processes in many fields of biomedical research. The transgenic technology allows researchers to carry out specific genetic manipulation in all cells of a laboratory animal, and makes it possible to dissect gene function in a living organism. In the field of neurosciences these animals have contributed greatly to shed light on basic mechanisms of brain function as well as to generate useful animal models for studying human neurological disorders. In this review, the different techniques available for generating specific mutations in the mouse genome will be described, 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 additional approach to neuropharmacology will be discussed, not only for the study of molecular mechanisms in the central nervous system but also for the identification of new biological targets for innovative pharmacological therapy. (C) 1999 Academic Press.