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 the Brown Norway laboratory 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.