PUBLICATION
RPS24 haploinsufficiency impairs erythropoiesis in the Diamond-Blackfan anemia zebrafish model via the STAT6-SATB1 pathway
- Authors
- Ahn, S., Oh, C.K.
- ID
- ZDB-PUB-250310-2
- Date
- 2025
- Source
- Biochemical and Biophysical Research Communications 756: 151563151563 (Journal)
- Registered Authors
- Keywords
- Diamond–Blackfan anemia, Erythropoiesis, RPS24, SATB1, STAT6, Zebrafish
- MeSH Terms
-
- Gene Knockdown Techniques
- Haploinsufficiency*
- Anemia, Diamond-Blackfan*/genetics
- Anemia, Diamond-Blackfan*/metabolism
- Anemia, Diamond-Blackfan*/pathology
- STAT6 Transcription Factor*/genetics
- STAT6 Transcription Factor*/metabolism
- Zebrafish*/genetics
- Animals
- Ribosomal Proteins*/genetics
- Ribosomal Proteins*/metabolism
- Disease Models, Animal*
- Erythropoiesis*/genetics
- Signal Transduction*
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 40054062 Full text @ Biochem. Biophys. Res. Commun.
Citation
Ahn, S., Oh, C.K. (2025) RPS24 haploinsufficiency impairs erythropoiesis in the Diamond-Blackfan anemia zebrafish model via the STAT6-SATB1 pathway. Biochemical and Biophysical Research Communications. 756:151563151563.
Abstract
Diamond-Blackfan anemia (DBA) is a rare bone marrow failure disorder primarily caused by mutations in ribosomal proteins (RPs), including RPS24, leading to impaired erythropoiesis. Despite advances in our understanding of the roles of other RPs, the mechanisms underlying RPS24-related DBA remain unclear. Therefore, in this study, we aimed to investigate the effect of RPS24 haploinsufficiency on erythropoiesis using a zebrafish model. RPS24 knockdown via morpholino injection significantly reduced the hemoglobin levels, as confirmed by O-dianisidine staining and whole-mount in situ hybridization. Further analysis revealed that RPS24 deficiency downregulated the expression of SATB homeobox 1a (satb1a), a key regulator of erythroid differentiation, by inhibiting the signal transducer and activator of transcription 6 (STAT6) signaling pathway. Western blotting analysis revealed decreased levels of pSTAT6 correlated with the decrease in downstream erythroid marker levels. satb1a knockdown further impaired erythropoiesis in zebrafish, reinforcing its critical role in DBA pathogenesis. Overall, our findings suggest that RPS24 haploinsufficiency leads to DBA by disrupting the STAT6-SATB1 axis, providing novel insights into the molecular mechanisms underlying erythropoietic failure in DBA. Furthermore, this study highlights the importance of zebrafish models for further exploration of therapeutic targets for DBA.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping