The elevation of the humble mouse to become many scientists' experimental animal of choice has been one of the scientific phenomena of the last two decades. Today, genetically-altered mice are an essential component of the experimental toolkit, with thousands of varieties contributing to research in laboratories around the world. Their existence stems from discoveries made in the 1980's by this year's Nobel Laureates in Physiology or Medicine.
Mario Capecchi and Oliver Smithies were both seeking ways of specifically altering the mammalian genome, Capecchi with a view to inserting new genes into cells and Smithies in the hope of correcting genetic defects that lead to disease. Working against a background of skepticism, they independently discovered that they could use a natural mechanism, revealed decades before by Joshua Lederberg in bacteria, to introduce short sequences of manipulated DNA into the chromosomes of mammalian cells growing in the laboratory. The technique allowed them to target individual genes with exquisite precision, producing the genetic alterations they sought, but only at the cellular level. Happily, the embryonic stem cell cultures that Martin Evans was then developing provided the necessary vehicle for taking such gene manipulations from the Petri dish into the whole animal. Combining the two, by modifying genes in embryonic stem cells and then injecting those cells into fertilized mouse eggs, made it possible to rear mice with discrete genetic modifications that would be inherited between generations. The so-called 'Knock-out mouse' was born.
Knock-out (and knock-in) mice, the workhorses of many a laboratory today, allow researchers to study the effects of removing (or inserting) a single gene. Genetically-modified mice have therefore frequently helped to reveal a gene's function and, since mice and humans share a remarkable genetic similarity, they also serve as models of many human diseases.
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