Zebrafish Von Willebrand Factor Page: 1
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Carrillo, Maira M., Zebrafish von Willebrand Factor. Doctor of Philosophy
(Molecular Biology) August 2012, 101 pp., 22 figures, 150 numbered references.
In humans, von Willebrand factor (vWF) is a key component in hemostasis and
acts as a 'cellular adhesive' by letting the circulating platelets bind to exposed
subendothelium. It also acts as a carrier and stabilizer of factor VIII (FVIII). A
dysfunction or reduction of vWF leads to von Willebrand disease (vWD), resulting in
bleeding phenotype which affects 1% of the population. Currently there are a variety of
animal models used for the study of vWF and vWD; however, they do not possess the
advantages found in zebrafish. Therefore, we set out to establish zebrafish as a model
for the investigation of vWF and vWD through the use of bioinformatics and various
molecular techniques. Using bioinformatics we found that the vWF gene is located on
chromosome 18, that the GPlbp3 protein sequence is conserved. Confirmation of vWF
production was shown by means of immunostaining and by RT-PCR, in thrombocytes
as well as in veins and arteries. Evidence of vWF involvement in hemostasis and
thrombosis was shown using MO and VMO technology to produce a vWD like
phenotype, resulting in an increase in TTO and TTA, as well as a reduction in FVIII
when blood was tested using the kPTT assay, coinciding with a decrease in vWF.
Stimate treatment provided opposite results of MO and VMO, showing a decrease in
TTO and TTA. Investigation of the role of microparticles in hemostasis and their
interaction with vWF resulted in a conclusion that the GPlba receptor should exist on
MPs and that it may interact not only with zebrafish vWF but also with human UL-vWF.
Agglutination of MPs in the presence of UL-vWF but in the absence of ristocetin and
plasma, treatment with ADAMTS-13 abolishing the interaction between MPs and UL-
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Carrillo, Maira M. Zebrafish Von Willebrand Factor, dissertation, August 2012; Denton, Texas. (digital.library.unt.edu/ark:/67531/metadc177228/m1/2/: accessed December 16, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; .