Gp1ba, also known as glycoprotein 1bα, is a crucial component of the GPIb-IX-V complex on the platelet surface, which serves as the von Willebrand factor (VWF) receptor. This complex plays a vital role in platelet adhesion and activation, contributing to normal hemostasis [1,3]. Conditional knockout (CKO) mouse models, such as the Gp1ba-Cre transgenic mouse, are valuable for studying the specific functions of Gp1ba [4].

The Gp1ba-Cre transgenic mouse strain demonstrates more stringent megakaryocyte lineage-specific expression compared to the Pf4-Cre transgenic mouse, which has broader tissue expression. This allows for a better understanding of platelet functions in inflammation and other pathophysiological processes involving platelet-leukocyte interactions [4]. In zebrafish, gp1ba mutant models display a bleeding phenotype, macrothrombocytes similar to human GP1BA deficiency, and decreased ristocetin-mediated agglutination, suggesting an autosomal dominant mode of inheritance and modeling classical Bernard Soulier Syndrome [2]. Mutations in the human GP1BA gene are associated with Bernard-Soulier syndrome, a rare inherited macrothrombocytopenia characterized by prolonged bleeding, thrombocytopenia, and abnormally large platelets [1,3,5].

In conclusion, Gp1ba is essential for platelet-related functions, especially in hemostasis. Gene-knockout mouse models and zebrafish mutants have significantly contributed to understanding its role in normal biological processes and in diseases like Bernard-Soulier syndrome. These models provide insights into the underlying mechanisms, potentially guiding the development of targeted therapies for platelet-related bleeding disorders.

References:

1. Zhang, Senlin, Ling, Jing, Cui, Kai, Fan, Junjie, Hu, Shaoyan. 2024. Bernard-Soulier syndrome caused by two novel heterozygous GP1BA gene mutations: a case report and literature review. In Hematology (Amsterdam, Netherlands), 29, 2334642. doi:10.1080/16078454.2024.2334642. https://pubmed.ncbi.nlm.nih.gov/38564005/

2. Dhinoja, Sanchi, Al Qaryoute, Ayah, Fallatah, Weam, DeMaria, Anthony, Jagadeeswaran, Pudur. 2022. Characterization of zebrafish gp1ba mutant and modelling Bernard Soulier syndrome. In Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis, 33, 272-279. doi:10.1097/MBC.0000000000001135. https://pubmed.ncbi.nlm.nih.gov/35802508/

3. Skalníková, Magdalena, Staňo Kozubík, Kateřina, Trizuljak, Jakub, Pospíšilová, Šárka, Doubek, Michael. 2022. A GP1BA Variant in a Czech Family with Monoallelic Bernard-Soulier Syndrome. In International journal of molecular sciences, 23, . doi:10.3390/ijms23020885. https://pubmed.ncbi.nlm.nih.gov/35055070/

4. Nagy, Zoltan, Vögtle, Timo, Geer, Mitchell J, Mazharian, Alexandra, Senis, Yotis A. 2018. The Gp1ba-Cre transgenic mouse: a new model to delineate platelet and leukocyte functions. In Blood, 133, 331-343. doi:10.1182/blood-2018-09-877787. https://pubmed.ncbi.nlm.nih.gov/30429161/

5. Özdemir, Zeynep C, Düzenli Kar, Yeter, Ceylaner, Serdar, Bör, Özcan. . A novel mutation in the GP1BA gene in Bernard-Soulier syndrome. In Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis, 31, 83-86. doi:10.1097/MBC.0000000000000868. https://pubmed.ncbi.nlm.nih.gov/31789661/