The Anglo-Saxon term "knock-out" is used in pugilistic terms to describe a single blow that knocks the opponent in the ring. In biology used to refer to mice that have been modified gene. The importance of this technique is crucial because these mice analyzing knockout, we try to know the function of more than 25,000 genes. We must remember that 99% of mouse genes have counterparts in humans, so this knowledge will have important implications for future medicine. The three researchers who have helped develop this methodology have recently been awarded the Nobel Prize. The development of mice "knockout" had to solve two major challenges: first, changes or mutations occur in a given gene in cultured cells, the second pass this mutation into the mouse germ line to allow the development of these animals. The first problem was solved independently by two U.S. researchers, Oliver Smithies and Mario R Capecchi. Took advantage of a natural mechanism called homologous recombination allows cells to repair exchange and the two homologous genes obtained from each parent. Designed fragments of modified genes interspersed in the genome cell replacing the original gene, the latest was the experimental design that allowed them to select the modified cells. The second major challenge was solved by the "third man", Martin J. Evans In 1981 he published his first paper on the establishment of stable lines of mouse embryonic cells obtained from embryos in the laboratory of the University of Cambridge. The meeting of these three researchers in 1985 was momentous in the history of biomedical research. The establishment of targeted mutations in embryonic stem cells using the methodology developed so far has allowed about 2,500 mice to obtain knockout, each containing in their cells for an altered gene, whose biological significance can be determined. Joint projects and programs (Nature Genetics vol. 36:921-927) seeking to unite the efforts multiple laboratories, mainly from USA, Canada and Europe propose to use this methodology to understand the relationship between the function of more than 25,000 genes with the onset of certain diseases
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