Forward genetic analysis of TLR-signaling pathways: an evaluation.
Forward genetic approaches have contributed to our understanding of how the host senses infectious agents such as bacteria, viruses and fungi. Beginning with the initial discovery of Toll-like receptors (TLRs) as primary sensors involved in the recognition of microbial components, our laboratory has taken a forward genetic approach, using N-ethyl-N-nitrosourea (ENU) mutagenesis in mice, to decipher TLR-signaling pathways. This long term effort has helped to elucidate the circuitry of these pathways, identified new molecules, and disclosed new functions for known molecules. Here we review some of the more important insights developed from this approach and discuss its prospects.
Hoebe
Kasper
K
Cincinnati Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Division of Molecular Immunology, Room S5.421, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA. kasper.hoebe@cchmc.org
Beutler
Bruce
B
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D005038:Ethylnitrosourea / Q000633:toxicity; D006801:Humans; D009153:Mutagens / Q000633:toxicity; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D051193:Toll-Like Receptors / Q000235:genetics* / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D009153:Mutagens; D051193:Toll-Like Receptors; D005038:Ethylnitrosourea