Gene targeting technology and advances in the pathophysiology of inflammation

Gene targeting ('knock-out') technology is now widely used in the basic science of all disciplines of pathology and particularly auto-immune and inflammatory disease. Gene targeting is the wilful introduction of precise mutations into the genome of an animal, usually a mouse, affecting the function of a single gene or genes. The phenotyping of knockout mice provides whole animal data on the functions of individual genes in pathophysiological settings, and frequently provides the basis for novel therapeutic strategies. 'Knock-ins', the Cre-LoxP system and conditional knockouts are important new advances. This paper serves as an introduction to the methodology and draws on examples of major advances in inflammation research provided by the targeting of cytokines, in particular the tumour necrosis factor family of ligands.