Wound-healing studies in transgenic and knockout mice.
Injury to the skin initiates a cascade of events including inflammation, new tissue formation, and tissue remodeling, that finally lead to at least partial reconstruction of the original tissue. Historically, animal models of repair have taught us much about how this repair process is orchestrated and, over recent years, the use of genetically modified mice has helped define the roles of many key molecules. Aside from conventional knockout technology, many ingenious approaches have been adopted, allowing researchers to circumvent such problems as embryonic lethality, or to affect gene function in a tissue- or temporal-specific manner. Together, these studies provide us with a growing source of information describing, to date, the in vivo function of nearly 100 proteins in the context of wound repair. This article focuses on the studies in which genetically modified mouse models have helped elucidate the roles that many soluble mediators play during wound repair, encompassing the fibroblast growth factor (FGF) and transforming growth factor-beta (TGF-beta) families and also data on cytokines and chemokines. Finally, we include a table summarizing all of the currently published data in this rapidly growing field. For a regularly updated web archive of studies, we have constructed a Compendium of Published Wound Healing Studies on Genetically Modified Mice which is avaialble at http://icbxs.ethz.ch/members/grose/woundtransgenic/home.html.
London Research Institute Lab 214, Cancer Research UK, 61 Lincoln's Inn Fields, London WC2A 3PX, UK. richard.grose@cancer.org.uk
Richard
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Grose
Sabine
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Werner
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000502:physiology; D007249:Inflammation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism; D013997:Time Factors; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014945:Wound Healing
D016207:Cytokines; C496454:Fgf7 protein, mouse; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors