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The first recorded knockout mouse was created by Mario R. Capecchi, Martin Evans, and Oliver Smithies in 1989, for which they were awarded the 2007 Nobel Prize in Physiology or Medicine. Aspects of the technology for generating knockout mice, and the mice themselves have been patented in many countries by private companies.
Conditional gene knockout is a technique used to eliminate a specific gene in a certain tissue, such as the liver. [1] [2] This technique is useful to study the role of individual genes in living organisms. It differs from traditional gene knockout because it targets specific genes at specific times rather than being deleted from beginning of life.
Example of a T-REx system controlling the expression of shRNA. Tetracycline-controlled transcriptional activation is a method of inducible gene expression where transcription is reversibly turned on or off in the presence of the antibiotic tetracycline or one of its derivatives (e.g. doxycycline).
Additionally, gene knockouts are not always a good model for human disease as the mouse genome is not identical to the human genome, and mouse physiology is different from human physiology. The KO technique is essentially the opposite of a gene knock-in. Knocking out two genes simultaneously in an organism is known as a double knockout (DKO).
The International Mouse Phenotyping Consortium (IMPC) is an international scientific endeavour to create and characterize the phenotype of 20,000 knockout mouse strains. [1] [2] [3] Launched in September 2011, [1] the consortium consists of over 15 research institutes across four continents with funding provided by the NIH, European national governments and the partner institutions.
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]
Mario Ramberg Capecchi (born 6 October 1937) is an Italian-born molecular geneticist and a co-awardee of the 2007 Nobel Prize in Physiology or Medicine for discovering a method to create mice in which a specific gene is turned off, known as knockout mice.
FGF15 is found in the absorptive cells of the mouse ileum and plays an important role in feedback inhibition of hepatic bile acid synthesis. [8] FGF15 (and FGF19 in humans) function as hormones produced in response to bile acid absorption acting on the farnesoid X receptor FXR, are secreted into the portal venous circulation and bind onto the liver membrane receptor FGFR4/β-Klotho and repress ...