Famciclovir leads to failure of hematopoiesis, but may have the benefit of relieving myeloid expansion in MDS-like zebrafish

Li, Jing; Meng, Panpan; Zhou, Riyang; Zhang, Yiyue; Lin, Qing

doi:10.1016/j.taap.2020.115334

Cited by 5 publications

(2 citation statements)

References 35 publications

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“…They have already been used as a model of human thrombocytopenia 29,30 . Zebrafish have also been used to perform high‐throughput drug screening using transgenic fish with fluorescent signals in various lineages of hematopoietic cells 31 . To illustrate the pathogenicity of human THPO mutations and evaluate the effect of THPO‐RAs, we generated a zebrafish thpo loss‐of‐function mutant ( thpo szy6 ) using CRISPR/Cas9 gene editing.…”

Section: Introductionmentioning

confidence: 99%

“…29,30 Zebrafish have also been used to perform high-throughput drug screening using transgenic fish with fluorescent signals in various lineages of hematopoietic cells. 31 To illustrate the pathogenicity of human THPO mutations and evaluate the effect of THPO-RAs, we generated a zebrafish thpo loss-of-function mutant (thpo szy6 ) using CRISPR/Cas9 gene editing. We demonstrated that thpo mutants developed thrombocytopenia because of the decreased expression of THPO.…”

Section: Introductionmentioning

confidence: 99%

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Generation of a thrombopoietin‐deficient thrombocytopenia model in zebrafish

Yang

Meng

et al. 2022

Journal of Thrombosis and Haemostasis

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Background The production of platelets is tightly regulated by thrombopoietin (THPO). Mutations in the THPO gene cause thrombocytopenia. Although mice lacking Thpo present with thrombocytopenia, predicting phenotypes and pathogenicity of novel THPO mutations in mice is limited. Zebrafish can be a powerful tool for fast validation and study of candidate genes of human hematological diseases and have already been used as a model of human thrombocytopenia. Objectives We aim to investigate the role of Thpo in zebrafish thrombopoiesis and to establish a Thpo‐deficient zebrafish model. The model could be applied for illustrating the clinically discovered human THPO variants of which the clinical significance is not known and to evaluate the effect of THPO receptor agonists (THPO‐Ras), as well as a screening platform for new drugs. Methods We generated a thpo loss‐of‐function zebrafish model using CRISPR/Cas9. After disruption of zebrafish thpo, thposzy6 zebrafish presented with a significant reduction of thpo expression and developed thrombocytopenia. Furthermore, we performed in vivo studies with zebrafish with the thposzy6 mutation and found two human clinical point mutations (c.091C > T and c.112C > T) that were responsible for the thrombocytopenia phenotype. In addition, effects of THPO‐RAs used as therapeutics against thrombocytopenia were evaluated in the Tg(mpl:eGFP);thposzy6 line. Results and conclusions Zebrafish with the mutation thposzy6 presented with a significant reduction of thpo expression and developed thrombocytopenia. Thpo loss‐of‐function zebrafish model can serve as a valuable preclinical model for thrombocytopenia caused by thpo‐deficiency, as well as a tool to study human clinical THPO variants and evaluate the effect of THPO‐RAs.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Generation of a thrombopoietin‐deficient thrombocytopenia model in zebrafish

Yang

Meng

et al. 2022

Journal of Thrombosis and Haemostasis

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Establishment of a Diamond‐Blackfan anemia like model in zebrafish

Ling,

Wu,

Liu

et al. 2024

Developmental Dynamics

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BackgroundAnemia is defined as a lack of erythrocytes, low hemoglobin levels, or abnormal erythrocyte morphology. Diamond‐Blackfan anemia (DBA) is a rare and severe congenital hypoplastic anemia that occurs due to the dominant inheritance of a ribosomal protein gene mutation. Even rarer is a case described as Diamond‐Blackfan anemia like (DBAL), which occurs due to a loss‐of‐function EPO mutation recessive inheritance. The effective cures for DBAL are bone marrow transfusion and treatment with erythropoiesis‐stimulating agents (ESAs). To effectively manage the condition, construction of DBAL models to identify new medical methods or screen drugs are necessary.ResultsHere, an epoa‐deficient mutant zebrafish called epoaszy8 was generated to model DBAL. The epoa‐deficiency in zebrafish caused developmental defects in erythroid cells, leading to severe congenital anemia. Using the DBAL model, we validated a loss‐of‐function EPO mutation using an in vivo functional analysis and explored the ability of ESAs to alleviate congenital anemia.ConclusionsTogether, our study demonstrated that epoa deficiency in zebrafish leads to a phenotype resembling DBAL. The DBAL zebrafish model was found to be beneficial for the in vivo assessment of patient‐derived EPO variants with unclear implications and for devising potential therapeutic approaches for DBAL.

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