Key words :
embryonic stem cells,
2007 Nobel Prize in Physiology or Medicine: Knockout Mice
9 Oct, 2007 11:09 am
The winners of the 2007 Nobel Prize in Physiology or Medicine were announced this morning.
From the official press release:
This year's Nobel Laureates have made a series of ground-breaking discoveries concerning embryonic stem cells and DNA recombination in mammals. Their discoveries led to the creation of an immensely powerful technology referred to as gene targeting in mice. It is now being applied to virtually all areas of biomedicine - from basic research to the development of new therapies.
Gene targeting is often used to inactivate single genes. Such gene "knockout" experiments have elucidated the roles of numerous genes in embryonic development, adult physiology, aging and disease. To date, more than ten thousand mouse genes (approximately half of the genes in the mammalian genome) have been knocked out. Ongoing international efforts will make "knockout mice" for all genes available within the near future.
With gene targeting it is now possible to produce almost any type of DNA modification in the mouse genome, allowing scientists to establish the roles of individual genes in health and disease. Gene targeting has already produced more than five hundred different mouse models of human disorders, including cardiovascular and neuro-degenerative diseases, diabetes and cancer.
The first reports in which homologous recombination in ES cells was used to generate gene-targeted mice were published in 1989. Since then, the number of reported knockout mouse strains has risen exponentially. Gene targeting has developed into a highly versatile technology. It is now possible to introduce mutations that can be activated at specific time points, or in specific cells or organs, both during development and in the adult animal.
Almost every aspect of mammalian physiology can be studied by gene targeting. We have consequently witnessed an explosion of research activities applying the technology. Gene targeting has now been used by so many research groups and in so many contexts that it is impossible to make a brief summary of the results.
This last paragraph gets at an issue that I brought up in a post last month about some of the arguments used by opponents of animal research in the UK. Specifically, some were claiming that animal research was increasing in academia, despite the fact that industry had been able to curtain its use of animals. This implied that academics were using animal research recklessly and needlessly--a charge that is absolutely false. While the number of animal experiments performed in British academia had increased by 52% over the last ten years, this increase hadn't even kept up with the expansion of science in general in the UK (science funding had more than doubled during that period).
Regardless, this 52% increase can be almost solely attributed to the increasing use of knockout and knock-in animals (see the earlier post for details). Today's Nobel Prize announcement helps emphasize the importance of this research and further detracts from argument that such research is unnecessary or unjustifiable.
Check out Terra Sigillata for more on the Prize and how the predictions stacked up.
Jim Hu at Blogs for Industry also has an informative post about the prize.
From: The Scientific Activist
Key words :
embryonic stem cells,
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" the HAT (hypoxanthine aminopterin thymidine) selection for hprt+ tk+ cells developed by Waclaw Szybalski, Smithies' Wisconsin colleague years before ", in 1982.
The first transfection of mammalian (human) cells was accomplished and documented by Waclaw Szybalski in 1962, using HPRT gene, as published in PNAS.
Szybalska, E.H., Szybalski, W., 1962. Genetics of human cell lines. IV. DNA mediated heritable transformation of a biochemical trait. Proc. Natl. Acad. Sci. 48, 2026-2034.
Szybalski, W., 1992. Roots: Use of the HPRT gene and the HAT selection technique in DNA-mediated transformation of mammalian cells: first steps toward developing hybridoma techniques and gene therapy. BioEssays 14, 495-500.
Szybalski, W., 1991. A forerunner of monoclonal antibodies and human gene therapy (This Week's Citation Classic. Szybalska, E.H., Szybalski, W., Genetics of human cell lines. IV. DNA-mediated heritable transformation of a biochemical trait. Proc. Natl. Acad. Sci., U.S.A. 48, 2026-2034. Current Contents 34 No. 46, 11, 1991.