| Autor: |
Ling, Yiming, Wu, Jiaye, Liu, Yushi, Meng, Panpan, Sun, Ying, Zhao, Dejian, Lin, Qing |
| Předmět: |
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| Zdroj: |
Developmental Dynamics; Oct2024, Vol. 253 Issue 10, p906-921, 16p |
| Abstrakt: |
Background: Anemia 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. Results: Here, 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. Conclusions: Together, 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. Key Findings: This study confirmed the potential of the epoa‐deficient zebrafish model to provide valuable insights into the study of DBAL and effects of ESAs.The epoaszy8 zebrafish model accurately portrayed the severe congenital anemia associated with DBAL and showed that ESAs like rHuEPO were able to rescue the anemia. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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