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PHYSIOLOGICAL REVIEWS Vol. 78 No. 4 October 1998,
pp. 1131-1163
Copyright ©1998 The American Physiological Society
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; and Department of Cardiology, Children's Hospital, Harvard Medical School, Boston, Massachusetts
Picciotto, Marina R., and Kevin Wickman. Using Knockout and Transgenic Mice to Study Neurophysiology and Behavior. Physiol. Rev. 78: 1131-1163, 1998. 
Reverse genetics, in which detailed knowledge of a gene of interest permits in vivo modification of its expression or function, provides a powerful method for examining the physiological relevance of any protein. Transgenic and knockout mouse models are particularly useful for studies of complex neurobiological problems. The primary aims of this review are to familiarize the nonspecialist with the techniques and limitations of mouse mutagenesis, to describe new technologies that may overcome these limitations, and to illustrate, using representative examples from the literature, some of the ways in which genetically altered mice have been used to analyze central nervous system function. The goal is to provide the information necessary to evaluate critically studies in which mutant mice have been used to study neurobiological problems.
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