Smithies, Capecchi and Evans made an important contribution to modern science by helping to create the first “transgenic mouse” in the early 1980’s. By combining mutagenesis, using homologous recombination (interchanging a segment in the DNA with a similar segment), and cells proliferation, using embryonic stem cells (ES cells), they developed a method for creating mice bearing any desired mutation. Capecchi and Smithies showed separately that the mechanism of homologous recombination can be used to mutate specific genes. Evans created mosaic embryos by transplanting ES cells from one mouse into another mouse’s embryo, setting the cornerstones for creating an engineered mouse genome. The findings from these research projects lead to the development of the transgenic mouse.
The importance of the transgenic mouse in modern life sciences can not be exaggerated. Since the mouse is a common and effective model for studying human diseases, a thorough understanding of the mouse’s biology serves as an important tool for understanding, and ultimately for curing human diseases. One common way of studying mice is by ‘knocking out’ one of the mouse’s genes and then studying the phenotype of the “knockout” (KO) mouse. The KO is carried out using the method developed by Smithies, Capecchi and Evans. Another way of using transgenic mice is replacing a gene with a gene of the same type that is attached to a fluorescent reporter. This ‘tagging’ of the gene allows the researchers to track the exact location of a product of the gene in the mouse’s tissues, a method commonly used in brain research. Another important implementation of the fluorescent reporter method is in introducing foreign genes into the mouse’s genome in order to recreate a situation resembling that caused by a specific disease. A better understanding of the mouse’s biology and new models for certain diseases can help scientists understand human biology better.
TFOT covered the 2006 Nobel Prize in Medicine as well, shared by Andrew Z. Fire and Craig C. Mello for their discovery of the RNA interference (RNAi) process. The discovery, published in 1998, was that double-stranded RNA triggers suppression of gene activity in a homology-dependent manner.
Image: Capecchi (left), Evans (center) and Smithies (right) (Credit: Nobel Foundation)..
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