PUBLICATION
Transcriptomic analysis reveals mitochondrial dysfunction in the pathogenesis of Nager syndrome in sf3b4-depleted zebrafish
- Authors
- Ulhaq, Z.S., Tse, W.K.F.
- ID
- ZDB-PUB-240321-6
- Date
- 2024
- Source
- Biochimica et biophysica acta. Molecular basis of disease 1870(4): 167128 (Journal)
- Registered Authors
- Ulhaq, Zulvikar Syambani
- Keywords
- Craniofacial malformation, Mitochondrial complex I, Oxidative stress, RNA sequencing, Reactive oxygen species (ROS)
- MeSH Terms
-
- Animals
- Gene Expression Profiling
- Humans
- Mandibulofacial Dysostosis*
- Mitochondrial Diseases*
- Mutation
- RNA Splicing Factors/genetics
- Zebrafish*/genetics
- PubMed
- 38508476 Full text @ BBA Molecular Basis of Disease
Citation
Ulhaq, Z.S., Tse, W.K.F. (2024) Transcriptomic analysis reveals mitochondrial dysfunction in the pathogenesis of Nager syndrome in sf3b4-depleted zebrafish. Biochimica et biophysica acta. Molecular basis of disease. 1870(4):167128.
Abstract
Nager syndrome (NS) is a rare acrofacial dysostosis caused by heterozygous loss-of-function variants in the splicing factor 3B subunit 4 (SF3B4). The main clinical features of patients with NS are characterized by facial-mandibular and preaxial limb malformations. The migration and specification of neural crest cells are crucial for craniofacial development, and mitochondrial fitness appears to play a role in such processes. Here, by analyzing our previously published transcriptome dataset, we aim to investigate the potential involvement of mitochondrial components in the pathogenesis of craniofacial malformations, especially in sf3b4 mutant zebrafish. We identified that oxidative phosphorylation (OXPHOS) defects and overproduction of reactive oxygen species (ROS) due to decreased antioxidants defense activity, which leads to oxidative damage and mitochondrial dysfunction. Furthermore, our results highlight that fish lacking sf3b4 gene, primarily display defects in mitochondrial complex I. Altogether, our findings suggest that mitochondrial dysfunction may contribute to the development of the craniofacial anomalies observed in sf3b4-depleted zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping