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Americans Mario R. Capecchi (University of Utah; Howard Hughes Medical Institute) and Oliver Smithies (University of North Carolina) along with their British collaborator Martin J. Evans (Cardiff University) share the Nobel Prize in Physiology or Medicine 2007 “for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells" (see Nobelprize.org).

 

The trio developed a technique known as gene targeting which enabled them to introduce specific genetic modifications into mice through the use of embryonic stem cells. The basic technique involves introducing a targeted DNA fragment into mouse embryonic stem cells by a process called homologous recombination. These modified cells are then injected into an early mouse embryo (blastocyst) which is implanted into a female mouse. The resulting offspring are genetic chimeras which can subsequently be mated to normal mice to produce genetically modified offspring, often known as ‘knockout’ mice. Further development of this versatile technique has resulted in so-called ‘knock-in’ technology which also be used to replace an existing gene with another, or to introduce specific mutations.

 

The Nobel committee said that “their discoveries led to the creation of an immensely powerful technology … now being applied to virtually all areas of biomedicine – from basic research to the development of new therapies.” Since the production of the first knock-out mouse in the late 1980’s, gene targeting has become enormously widespread. Sequencing of both the human and mouse genomes in the early part of this century revealed that 99% of mouse genes have homologues in human, and in 2005, the National Institutes for Health (NIH) instigated the Knockout Mouse Project to generate a comprehensive source of mouse embryonic stem cells containing every possible gene knockout. Although gene targeting is not without its technical limitations and ethical difficulties, knockout mice have become an indispensible tool in biomedical research by providing experimental models of development and disease.