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A knockout mouse, or knock-out mouse, is a genetically modified mouse (Mus musculus) in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA.
Gene knockout by mutation is commonly carried out in bacteria. An early instance of the use of this technique in Escherichia coli was published in 1989 by Hamilton, et al. [2] In this experiment, two sequential recombinations were used to delete the gene.
In 1993 the first C57BL/6 gene targeted knockout mouse was published by a group at Hoffmann-La Roche in Switzerland. [10] In 2013 C57BL/6 mice were flown into space aboard Bion-M No.1. [11] In 2015 C57BL/6NTac females provided by Taconic Biosciences were sent to the International Space Station on SpaceX CRS-6. [12]
Conditional gene knockout is a time-consuming procedure and there are additional projects focusing on knocking out the remaining mouse genes. [6] The KOMP project contributor, Oliver Smithies , arguably provided the biggest scientific impact on this gene targeting.
Gene knock-in originated as a slight modification of the original knockout technique developed by Martin Evans, Oliver Smithies, and Mario Capecchi.Traditionally, knock-in techniques have relied on homologous recombination to drive targeted gene replacement, although other methods using a transposon-mediated system to insert the target gene have been developed. [3]
The International Knockout Mouse Consortium (IKMC) is a scientific endeavour to produce a collection of mouse embryonic stem cell lines that together lack every gene in the genome, and then to distribute the cells to scientific researchers to create knockout mice to study.
The Cre-Lox system is widely used to manipulate gene expression in model organisms such as mice in order to study human diseases and drug development. [3] For example, using the Cre-Lox system, researchers are able to study oncogenes and tumor suppressor genes and their role in the development and progression of cancer in mouse models. [4]
Capecchi was awarded the Nobel prize for creating a knockout mouse. This is a mouse, created by genetic engineering and in vitro fertilization, in which a particular gene has been turned off. [28] For this work, Capecchi was awarded the 2007 Nobel prize for medicine or physiology, along with Martin Evans and Oliver Smithies, who also contributed.
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