Writing Assignment 3
Humanized GPIbα-von Willebrand factor interaction in the mouse is a primary article about research conducted to better understand von Willebrand factor (VWF) interactions. Von Willebrand factor is a type of protein found in blood that attaches itself to platelets to assist in forming blood clots at a site of injury (CDC, 2021). Nearly one percent of people in the United States have VWF deficiency, which is known as Von Willebrand Disease (VWD) (CDC, 2021). Additionally, platelet glycoprotein Ibα (GPIbα) is a glycoprotein that interacts with VWF to begin the process of clotting when an injury occurs (Kanaji et. al, 2018). Understanding VWF is incredibly important, and impactful. The study discussed in this review, addresses the lack of research, incompatibility of animal models, and introduces innovative techniques.
Von Willebrand factor is difficult to study because it is species specific, despite the commonality of many species having VWF they function very differently in each (Kanaji et. al, 2018). This results in a lack of animal models and thus equally lacks in pharmacologic inhibitor research. The study conducted by Sachiko Kanaji et. al had multiple integral steps for overcoming these research disparities. First, the species specificity needed to be bridged so that research done on the animals could apply to humans. They accomplished this by cross-breeding and replacement. This began with domains A1 and A2 in mice with VWF exon 28-encoding being replaced with the human homologous structures resulting in a M1HA strain (Kanaji et. al, 2018). Consequent cross-breeding with mice that had no glycoprotein Ibα resulted in a strain of mice, H1HA, which had human reactions during GPIbα and VWF binding (Kanaji et. al, 2018). This resulting strain allows for studies to be conducted that are relevant to human treatment of different bleeding disorders.
The next step within the study was to conduct experiments on the mice to collect new data. To determine the implications of the removal and addition of different glycoproteins and VWF’s the researchers removed three mm of each strain's tail and submerged the wound in solution at 37 degrees Celsius (Kanaji et. al, 2018). The bleed time was recorded up to 600 seconds, approximately ten minutes, and then the wound was cauterized. The resulting data showed that the strains with human glycoprotein or VWF reciprocals that lacked either the glycoprotein or VWF showed a greatly increased bleed time than wild-type mice or those with human reciprocals that have the matching factors (Kanaji et. al, 2018). It is important to highlight a note the researchers discussed briefly. While this animal model is very effective and innovative, concerns such as TTP (thrombotic thrombocytopenic purpura), which is a blood disorder that could present due to the stress in mice, need to be addressed in subsequent studies.
In conclusion, while the study does require repetition and refinement the results are very promising. This study provides an outline for altering animal models in cases of species specificity which can be applied to any number of human health studies. Additionally, it gave encouraging results for the experimental structures application to von Willebrand factor studies. The continued research on this could expand the understanding and treatment of different bleeding disorders, including those resulting from von Willebrand factor deficiency.
References:
Kanaji, S. et al. Humanized GPIbα-von Willebrand factor interaction in the mouse. Blood Adv 2 (19), 2522-2532 (2018).
What is von Willebrand disease? Centers for Disease Control and Prevention (2021). Available at: https://www.cdc.gov/ncbddd/vwd/facts.html. (Accessed: 29th September 2022)
By: Joy Brewer
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