Although the role of APC in the initiation of human colorectal cancer is well established, its role in other tissue and developmental processes are not well understood. Given the importance of regulation of Wnt signaling in embryonic pattern formation and morphogenesis of many organs, mechanistic understanding of APC in development and in extracolonic tissues becomes critical to better assess potential adverse events in humans. One approach to understand the role of Apc in development is to develop mice with an inactivating Apc mutation. Several genetically modified mouse strains for Apc have been described [7–10]. Most of these models, in the heterozygous state, show a gastrointestinal and other tumor predisposition phenotype [7–10]. Mouse embryos that are homozygous for the genetic modification die during embryogenesis, and some of the models do not survive beyond gastrulation [8,11]. An alternate approach to understand the role of Apc in development and/or in specific tissues is to generate a mouse strain that carries a conditionally modified allele and mate it with a mouse strain that facilitates the modification of the conditional allele in specific cell lineages.