A powerful and versatile tool to study embryonic development is genetic manipulation. The effect that mutations have on development facilitates an understanding of the underlying mechanisms in the same way that throwing a wrench into an engine can reveal the importance of the crankshaft. Although the connection between the part (or gene) affected and the eventual result is not always obvious, persistent tampering and observing the effect of combining one mutant with another will reveal the elegant workings of the" machinery." The evidence for the success of applying random mutagenesis to dissecting developmental pathways is ample, and to realize this one needs only to read through a review describing Drosophila or C. elegans development. l'2 However, using traditional genetic methodologies with mammals is difficult due to their long generation time and the complexity of the genome. Therefore, those wishing to study genes important in mammalian development have had to rely mainly on the" reverse genetic" approach to isolate genes by sequence similarity and subsequent genetic analysis via homologous recombination) Although these methodologies have certainly not been exhausted, an approach directed toward random mutagenesis will expand the base of genes to study. t L. Cooley, R. Kelley, and A. Spradling, Science 239, 121 (1988). 2 IA Hope, Deoelopment (Cambridge, UK) 113, 399 (1991). 3 A. Bradley, Curr. Opin. Biotechnol. 2, 823 (1991).