Pluripotent embryonic stem (ES) cells were developed as a tool for introducing specific, site-directed alterations into the mammalian genome to create mouse models in which gene function and regulation can be studied. ES cell lines are derived in vitro from the outgrowth of the inner cell mass (ICM) of a blastocyst, the portion of the blastocyst that gives rise to the embryo. Undifferentiated ES cells are then manipulated in culture and, when injected into a blastocyst, have the ability to incorporate back into the ICM and contribute to the genetic makeup of the developing embryo. The resulting pups are considered chimeric in their genetic makeup as they consist of tissues deriving from both the ES cells and cells within the ICM of the blastocyst. The desired outcome is to create chimeric mice that inherit germ cells derived from the injected ES cells. In this way, mutations can be introduced into the ES cells in vitro, then incorporated in vivo into the germline of a mouse and transmitted from generation to generation.
The 2008 Nobel Prize in medicine was given to three scientist, Drs Martin Evans, Mario Capecchi and Oliver Smithies, for their pioneering work on creating “knockout mice.”