Thpo, also known as thrombopoietin, is an essential cytokine for hematopoietic stem cell (HSC) maintenance and megakaryocyte differentiation [4]. It functions within the THPO-MPL pathway, which is crucial for normal hematopoiesis [1]. Disturbances in this pathway can lead to various bone marrow-related disorders. Genetic models, such as zebrafish models, can be valuable tools for studying Thpo [5].

Germline mutations of Thpo have been reported as causes of hereditary thrombocythemia. These mutations lead to increased production of Thpo protein through mechanisms like exon 3 skipping or base deletions that affect upstream suppressive open reading frames [2]. On the other hand, monoallelic loss-of-function Thpo variants cause heritable thrombocytopenia [3]. A zebrafish Thpo-deficient model showed that disruption of Thpo led to reduced Thpo expression and thrombocytopenia, and was used to study human clinical Thpo variants and evaluate Thpo-receptor agonists [5].

In conclusion, Thpo plays a vital role in hematopoiesis, especially in platelet production. Studies using models like the Thpo-deficient zebrafish have revealed its role in thrombocytopenia and thrombocythemia. Understanding Thpo's functions through these models provides insights into the mechanisms of these blood-related diseases, potentially guiding future diagnostic and therapeutic strategies.