TRANSGENIC AND KNOCKOUT ANALYSES OF THE ROLE OF TNF IN IMMUNE REGULATION AND DISEASE PATHOGENESIS

Transgenic mutagenesis in whole animals has become without doubt the m ost rewarding approach to analyse gene structure, expression, and func tion. In the TNF field, much of what we now question about TNF/TNF rec eptor function is based, to a large extent, on what we have already le arned by overexpressing these molecules in transgenic mice or by ablat ing their expression in knockout systems. In addition, a clearer view of the involvement of these molecules in disease pathogenesis has emer ged, and useful models for human disease have been generated. In this overview we summarise our experience with TNF transgenic and knockout systems, and highlight advances made in our understanding of the role played by TNF and its receptors in immune regulation and in the pathog enesis of infectious, inflammatory, and autoimmune disease. (C) 1996 W iley-Liss, Inc.