Gene and Enhancer Trapping: Mutagenic Strategies for Developmental Studies

This chapter discusses the merits and drawbacks of the use of mutagenic strategies in mouse that have been used in developmental systems. These approaches include the analysis of spontaneous mutations, chemical mutagenesis, and insertional mutagenesis, using transgenes, retroviruses or transposons, and trapping vectors; these approaches are compared with an emphasis on the potential, for using gene and enhancer trapping to dissect mammalian development. by far the most frequent mutagenic strategy used in systems other than mammals is chemical mutagenesis. It has been used to generate a high frequency of mutations in a relatively random manner. Several technical advances provide alternatives to chemical mutagenesis in higher organisms. These advances allow the insertion of foreign pieces of DNA into the genome of an organism of choice, and in some cases these insertional events may lead to mutations in endogenous genes. One strategy that appears to be particularly promising in mammals, the enhancer or promoter trap, has been borrowed from “lower” systems. This strategy is a natural extension of insertional mutagenesis, in which the insertional element also contains a reporter gene whose activity can be analyzed after the insertion into the chromosome.