Gene targeting studies: New methods, old problems

Abstract

Techniques to create transgenic organisms or animals with targeted mutations ('knock-out' mutants) have become increasingly important tools in the neurosciences over the last few years. As always, new techniques, besides providing new tools to investigate problems or to test hypotheses, also give rise to unforeseen difficulties and it takes some time for researchers to become aware of this. Gene targeting techniques provide no exception and Gerlai's1 alert is very timely indeed. The complications described by Gerlai are, not very surprisingly, strongly reminiscent of those encountered in the study of spontaneous mutations in the mouse. In that field congenic strains have been used since many years2. Congenic strains are obtained by repeatedly backcrossing a mutant to an inbred strain. If we now consider the possible complications that may be encountered with this approach we may, in fact, distinguish two rather different types of 'background' effects. As I will show in the following, the distinction between the two is crucial.