Conditional knockout mouse models of cancer.

Abstract

In 2007, three scientists, Drs. Mario R. Capecchi, Martin J. Evans, and Oliver Smithies, received the Nobel Prize in Physiology or Medicine for their contributions of introducing specific gene modifications into mice. This technology, commonly referred to as gene targeting or knockout, has proven to be a powerful means for precisely manipulating the mammalian genome and has generated great impacts on virtually all phases of mammalian biology and basic biomedical research. Of note, germline mutations of many genes, especially tumor suppressors, often result in lethality during embryonic development or at developmental stages before tumor formation. This obstacle has been effectively overcome by the use of conditional knockout technology in conjunction with Cre-LoxP- or Flp-Frt-mediated temporal and/or spatial systems to generate genetic switches for precise DNA recombination. Currently, numerous conditional knockout mouse models have been successfully generated and applied in studying tumor initiation, progression, and metastasis. This review summarizes some conditional mutant mouse models that are widely used in cancer research and our understanding of the possible mechanisms underlying tumorigenesis.