PUBLICATION
Establishment of a Diamond-Blackfan anemia like model in zebrafish
- Authors
- Ling, Y., Wu, J., Liu, Y., Meng, P., Sun, Y., Zhao, D., Lin, Q.
- ID
- ZDB-PUB-240308-1
- Date
- 2024
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists 253(10): 906-921 (Journal)
- Registered Authors
- Lin, Qing
- Keywords
- DBAL, epoa, zebrafish
- MeSH Terms
-
- Erythropoiesis
- Mutation
- Erythropoietin/genetics
- Erythropoietin/metabolism
- Zebrafish*
- Animals
- Disease Models, Animal*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Anemia, Diamond-Blackfan*/genetics
- Anemia, Diamond-Blackfan*/therapy
- PubMed
- 38450920 Full text @ Dev. Dyn.
Citation
Ling, Y., Wu, J., Liu, Y., Meng, P., Sun, Y., Zhao, D., Lin, Q. (2024) Establishment of a Diamond-Blackfan anemia like model in zebrafish. Developmental Dynamics : an official publication of the American Association of Anatomists. 253(10):906-921.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping