Genetic ablation in transgenic mice.

The study of mammalian development has very quickly moved from a largely descriptive endeavour to one in which very precise mechanistic questions can now be formulated and answered. Undoubtedly, advances in this area have been the result of a strong foundation in experimental embryology, the application of molecular genetic techniques to the isolation and analysis of genes of developmental interest, and the ability to manipulate genetically the embryo through transgenic mouse technology. Perhaps the most dramatic illustration of the power of these new technologies is the potential ability to generate mice either that carry mutations in virtually any gene in the germ line through gene targeting in totipotent embryonic stem (ES) cells or that lack specific cell types through the genetic ablation technology reviewed here. Together, these two approaches have made it possible to knock out either a specific gene or a specific cell type in an intact animal and thus offer almost unlimited possibilities for addressing questions concerning the molecular and cellular biology of development. As well, animal models for various human diseases such as dwarfism, immunodeficiencies and demyelination can now be generated. It is clear that further refinements in both gene targeting and genetic ablation technologies are necessary before the full potential of either approach will be realized. Further development of conditional or inducible ablation strategies, coupled with a more precise definition of the cis-acting sequences, responsible for directing gene expression in fully differentiated and more primitive cells, will greatly broaden the range of questions that can be addressed by this approach.(ABSTRACT TRUNCATED AT 250 WORDS)