|
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.〔Abbott A: Laboratory animals: the Renaissance rat. Nature 2004, 428:464-466.〕〔Zhou Q, Renard JP, Le Friec G, Brochard V, Beaujean N, Cherifi Y, Fraichard A, Cozzi J: Generation of fertile cloned rats by regulating oocyte activation. Science 2003, 302:1179.〕〔Justice MJ, Noveroske JK, Weber JS, Zheng B, Bradley A: Mouse ENU mutagenesis. Hum Mol Genet 1999, 8:1955–1963.〕〔Kitada K, Ishishita S, Tosaka K, Takahashi R, Ueda M, Keng VW, Horie K, Takeda J: Transposon-tagged mutagenesis in the rat. Nat Methods 2007, 4:131-133.〕 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'').〔Rat Genome Sequencing Project Consortium, Genome sequence of the brown rat yields insights into mammalian evolution. Nature, 2004. 428(6982): p. 493-521.〕 Additional developments with zinc finger nuclease technology in 2009 led to the first knockout rat with targeted, germline-transmitted mutations.〔Guerts, A.M., et. al, Knockout Rats via Embryo Microinjection of Zinc-Finger Nucleases. Science. Vol 325: 433 (24 July 2009) 〕 Knockout rat disease models for Parkinson's, Alzheimer's, hypertension, and diabetes using zinc-finger nuclease technology are being commercialized by SAGE Labs.〔Wiecek, Andrew. ("Year of the rat" ), ''BioTechniques'', 2009-10-01.〕〔("Sigma-Aldrich develops Parkinson's disease models" ), ''LaboratoryTalk''〕 ==Research use== Mice, rats, and humans share all but approximately 1% of each other's genes〔〔International Human Genome Sequencing Consortium, Initial sequencing and analysis of the human genome. Nature, 2001. 409(6822): p. 860-921.〕〔Mouse Genome Sequencing Consortium, Initial sequencing and comparative analysis of the mouse genome. Nature, 2002. 420(6915): p. 520-62.〕 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.〔Abbott, A., Laboratory animals: the Renaissance rat. Nature, 2004. 428(6982): p. 464-6.〕 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.〔Lindblad-Toh, K., Genome sequencing: three's company. Nature, 2004. 428(6982): p. 475-6.〕 Their larger size makes rats more conducive to study by instrumentation, and also facilitates manipulation such as blood sampling, nerve conduction, and performing surgeries. Techniques for genetic manipulation are available in the mouse, which is commonly used to model human disease. Although published knockouts exist for approximately 60%〔Zambrowicz, 1998; Skarnes et al., 2004; To et al., 2004; Nord et al., 2006〕 of mouse genes, a large majority of common human diseases do not have a knockout mouse model. Knockout rat models are an alternative to mice that may enable the creation of new gene disruptions that are unavailable in the mouse. Knockout rat models can also complement existing transgenic mouse models. Comparing mouse and rat mutants can facilitate the distinction between rodent-specific and general mammalian phenotypes. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Knockout rat」の詳細全文を読む スポンサード リンク
|