Open AccessEstablishment of a Bernard-Soulier syndrome model in zebrafish
Author(s) -
Qing Lin,
Rui Zhou,
Panpan Meng,
Liangliang Wu,
Lian Yang,
Wenyu Liu,
Jiaye Wu,
Yuanxiong Cheng,
Linjuan Shi,
Yiyue Zhang
Publication year - 2021
Publication title -
haematologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.782
H-Index - 142
eISSN - 1592-8721
pISSN - 0390-6078
DOI - 10.3324/haematol.2021.278893
Subject(s) - zebrafish , bernard–soulier syndrome , hemostasis , thrombopoiesis , biology , platelet , bleeding time , platelet disorder , pathogenesis , progenitor cell , bioinformatics , medicine , immunology , genetics , gene , stem cell , platelet aggregation , megakaryocyte
Platelets play an essential role in thrombosis and hemostasis. Abnormal hemostasis can cause spontaneous or severe post-traumatic bleeding. Bernard-Soulier syndrome (BSS) is a rare inherited bleeding disorder caused by a complete quantitative deficiency in the GPIb-IX-V complex. Multiple mutations in GP9 lead to the clinical manifestation of BSS. Understanding the roles and underlying mechanisms of GP9 in thrombopoiesis and establishing a proper animal model of BSS would be valuable to understand the disease pathogenesis and to improve its medical management. Here, by using CRISPR-Cas9 technology, we created a zebrafish gp9SMU15 mutant to model human BSS. Disruption of zebrafish gp9 led to thrombocytopenia and a high bleeding tendency, as well as an abnormal expansion of progenitor cells. The gp9SMU15 zebrafish can be used as a BSS animal model as GP9 roles in thrombocytopoiesis are highly conserved from zebrafish to mammals. Utilizing the BSS model, we verified the clinical GP9 mutations by in vivo functional assay and tested clinical drugs for increasing platelets. Thus, the inherited BSS zebrafish model could be of benefit for in vivo verification of patient-derived GP9 variants of uncertain significance and for potential BSS therapeutic strategy development.