Content area
Full Text
Complex as it is, much of the vast network of cellular functions has been successfully dissected, on a microscopic scale, by the use of mutants in which one element is altered at a time. A similar approach nay be fruitful in tackling the complex structures and events underlying behavior, using behavioral mutations to indicate modifications of the nervous system.
--Seymour Benzer(1, p. 1112)
Although complex behaviors are generally assumed to be under polygenic control, a handful of behaviors, especially among invertebrates, are profoundly regulated by single genes. In research pioneered by Benzer and colleagues in Drosophila(2, 3), examples of such genes include those influencing learning and memory(4), courtship behavior(5), and circadian rhythms(6, 7). At the same time, mouse genetics has had a longstanding tradition in behavioral analysis(8). Unlike the mutagenesis and screening approach favored in Drosophila, however, most mouse behavioral genetics has depended on natural variants and spontaneous mutants. Because genetic screens for specific behaviors have been rarely undertaken in the mouse, most neurological or behavioral mutants have obvious phenotypes (such as neuromuscular defects) or involve pleiotropic effects of coat color mutations(9). The cloning of such mutations was until recently a serendipitous endeavor, at best.
Recently, however, both forward and reverse genetic approaches have become feasible in the mouse. The revolution in transgenic(10-12) and gene targeting methods(13, 14) has opened the way for reverse genetic approaches to the study of behavior. Furthermore, forward genetic approaches have been developed in the mouse(15-18), and it is now feasible to isolate mutations of a desired class by chemical mutagenesis and screening procedures(19-21). The mapping and molecular identification of such induced mutations is now tractable with the development of high-density genetic linkage maps(22-25) and with the availability of substantial physical mapping and cloning resources in the mouse (Boxes 1 and 2)(25, 26). In many ways, mouse genetics now is at the threshold of discovery of behavioral mechanisms just as Drosophila genetics was in the 1970s. Both forward and reverse genetic approaches can be successfully applied to the mouse to analyze behavior.
BOX 1. GLOSSARY OF THE MOUSE GENOME
INBRED STRAIN. A set of animals that is produced by at least 20 consecutive generations of sister X brother or parent X offspring mating and that can be traced to a...