Knockout rat

A knockout rat is a genetically engineered rat with a single gene turned off through a targeted mutation (gene trapping) used for academic and pharmaceutical research. Knockout rats can mimic human diseases and are important tools for studying gene function (functional genomics) and for drug discovery and development. The production of knockout rats was not economically or technically feasible until 2008.

Technology developed through funding from the National Institutes of Health (NIH) and work accomplished by the members of the Knock Out Rat Consortium (KORC) led to cost-effective methods to create knockout rats. The importance of developing the rat as a more versatile tool for human health research is evidenced by the $120 million investment made by the NIH via the Rat Genome Sequencing Project Consortium, resulting in the draft sequence of a laboratory strain of the brown or Norway rat (Rattus norvegicus). Additional developments with zinc finger nuclease technology in 2009 led to the first knockout rat with targeted, germline-transmitted mutations. Knockout rat disease models for Parkinson's, Alzheimer's, hypertension, and diabetes using zinc-finger nuclease technology are being commercialized by SAGE Labs.

Mice, rats, and humans share all but approximately 1% of each other's genes making rodents good model organisms for studying human gene function. Both mice and rats are relatively small, easily handled, have a short generation time, and are genetically inbred. While mice have proven to be a useful rodent model and techniques have been developed for routine disruption of their genes, in many circumstances rats are considered a superior laboratory animal for studying and modeling human disease.

Rats are physiologically more similar to humans than are mice. For example, rats have a heart rate more similar to that of humans, while mice have a heart rate five to ten times as fast. It is widely believed that the rat is a better model than the mouse for human cardiovascular disease, diabetes, arthritis, and many autoimmune, neurological, behavioral, and addiction disorders. In addition, rat models are superior to mouse models for testing the pharmacodynamics and toxicity of potential therapeutic compounds, partially because the number and type of many of their detoxifying enzymes are very similar to those in humans. Their larger size makes rats more conducive to study by instrumentation, and also facilitates manipulation such as blood sampling, nerve conduction, and performing surgeries.

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