Cardiovascular and
cerebrovascular disease is the major cause of death in the developed world, with a high burden of disease and substantial pharmaceutical investment to manage it (WHO, Global Burden of Disease, 2004 Update, W.H. Organisation, Editor. 2008). Platelets, as the principal mediators of
thrombus formation, are a primary pharmaceutical target, with attenuation of platelet function and
thrombus formation significantly reducing the incidence of
myocardial infarction and
stroke. Haemostasis, however, may also be affected by antithrombotics, leading to spontaneous and/or prolonged
bleeding as a potentially severe side effect. Developing a comprehensive understanding of the mechanisms involved in platelet function and
thrombus formation is anticipated to identify drug targets that may effectively manage
vascular disease without an impact on haemostasis. Despite the progress in characterising individual genes in platelet function and
thrombosis, using gene knockout and transgenic mice over the past decade or so, there is still much to be uncovered. Investigating gene function using mouse models is a substantial investment and a considerable amount of work, with a relevant phenotype not guaranteed. As such, a new model is needed for the effective screening of novel genes that have been identified as having potential roles in platelet function or
cardiovascular disease by genomic association and comparative expression studies (Nature, 447(7145): 661-678, 2007;
Nat Genet, 41(11): 1182-1190, 2009; N Engl J Med, 357(5): 443-453, 2007; Blood, 109(8): 3260-3269, 2007). Here, we highlight and discuss the relevance of the zebrafish (Danio rerio) as a model for studying
thrombosis, the current techniques that are employed to assess gene function in a zebrafish model of
thrombosis, and how an effective genetic screen may be constructed.