Manipulating the germline: its impact on the study of carcinogenesis

Over the past two decades, the mouse has established itself as the primary organism in which to investigate the fundamental mechanisms of carcinogenesis and to model human neoplasia. The principal reason underlying such dominance almost certainly arises out of our ever increasing ability to manipulate the murine germline. Over the past 20 years we have moved from a position where animal models arose either spontaneously or were generated through exposure to carcinogen to a position in which it is possible to create and study precise mutations of choice. The most recent advances in inducible and conditional technologies now open the possibility for both temporal and tissue-specific gene manipulation. Each of these technological breakthroughs has facilitated significant steps forward in our understanding of the genetic basis of tumorigenesis. This review will highlight some of the major advances in the production and use of murine models of neoplasia over the last two decades.