A knockout mouse, or knock-out mouse, is a genetically modified mouse in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are important animal models for studying the role of genes which have been sequenced but whose functions have not been determined. By causing a specific gene to be inactive in the mouse, and observing any differences from normal behaviour or physiology, researchers can infer its probable function.

Mario Ramberg Capecchi 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. He shared the prize with Martin Evans and Oliver Smithies. He is currently Distinguished Professor of Human Genetics and Biology at the University of Utah School of Medicine.