PUBLICATION
FGF8 rescues motor deficits in zebrafish model of limb-girdle muscular dystrophy R18
- Authors
- Ulhaq, Z.S., Ogino, Y., Tse, W.K.F.
- ID
- ZDB-PUB-230226-32
- Date
- 2023
- Source
- Biochemical and Biophysical Research Communications 652: 768376-83 (Journal)
- Registered Authors
- Ulhaq, Zulvikar Syambani
- Keywords
- Epithelial-mesenchymal transition, FGF8, Fibrosis, LGMD R18, Notch, Trappc11
- MeSH Terms
-
- Animals
- Muscle, Skeletal/metabolism
- Muscular Diseases*/metabolism
- Muscular Dystrophies, Limb-Girdle*/genetics
- Mutation
- Zebrafish
- PubMed
- 36827861 Full text @ Biochem. Biophys. Res. Commun.
Citation
Ulhaq, Z.S., Ogino, Y., Tse, W.K.F. (2023) FGF8 rescues motor deficits in zebrafish model of limb-girdle muscular dystrophy R18. Biochemical and Biophysical Research Communications. 652:768376-83.
Abstract
Variants in the gene encoding trafficking protein particle complex 11 (TRAPPC11) cause limb-girdle muscular dystrophy R18 (LGMD R18). Although recently several genes related to myopathies have been identified, correlations between genetic causes and signaling events that lead from mutation to the disease phenotype are still mostly unclear. Here, we utilized zebrafish to model LGMD R18 by specifically inactivating trappc11 using antisense-mediated knockdown strategies and evaluated the resulting muscular phenotypes. Targeted ablation of trappc11 showed compromised skeletal muscle function due to muscle disorganization and myofibrosis. Our findings pinpoint that fish lacking functional trappc11 suppressed FGF8, which resulted in the aberrant activation of Notch signaling and eventually stimulated epithelial-mesenchymal transition (EMT) and fibrotic changes in the skeletal muscle. In summary, our study provides the role of FGF8 in the pathogenesis and its therapeutic potential of LGMD R18.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping