PUBLICATION
Modeling Sarcoglycanopathy in Danio rerio
- Authors
- Dalla Barba, F., Soardi, M., Mouhib, L., Risato, G., Akyürek, E.E., Lucon-Xiccato, T., Scano, M., Benetollo, A., Sacchetto, R., Richard, I., Argenton, F., Bertolucci, C., Carotti, M., Sandonà, D.
- ID
- ZDB-PUB-230827-52
- Date
- 2023
- Source
- International Journal of Molecular Sciences 24(16): (Journal)
- Registered Authors
- Argenton, Francesco, Bertolucci, Cristiano, Lucon-Xiccato, Tyrone, Risato, Giovanni
- Keywords
- animal models, genome editing, knockout, limb girdle muscular dystrophies, β-sarcoglycan, δ-sarcoglycan
- MeSH Terms
-
- Animals
- Drug Evaluation, Preclinical
- Endoplasmic Reticulum-Associated Degradation
- Larva
- Muscular Dystrophies, Limb-Girdle*
- Sarcoglycanopathies*
- Zebrafish/genetics
- PubMed
- 37628888 Full text @ Int. J. Mol. Sci.
Citation
Dalla Barba, F., Soardi, M., Mouhib, L., Risato, G., Akyürek, E.E., Lucon-Xiccato, T., Scano, M., Benetollo, A., Sacchetto, R., Richard, I., Argenton, F., Bertolucci, C., Carotti, M., Sandonà, D. (2023) Modeling Sarcoglycanopathy in Danio rerio. International Journal of Molecular Sciences. 24(16):.
Abstract
Sarcoglycanopathies, also known as limb girdle muscular dystrophy 3-6, are rare muscular dystrophies characterized, although heterogeneous, by high disability, with patients often wheelchair-bound by late adolescence and frequently developing respiratory and cardiac problems. These diseases are currently incurable, emphasizing the importance of effective treatment strategies and the necessity of animal models for drug screening and therapeutic verification. Using the CRISPR/Cas9 genome editing technique, we generated and characterized δ-sarcoglycan and β-sarcoglycan knockout zebrafish lines, which presented a progressive disease phenotype that worsened from a mild larval stage to distinct myopathic features in adulthood. By subjecting the knockout larvae to a viscous swimming medium, we were able to anticipate disease onset. The δ-SG knockout line was further exploited to demonstrate that a δ-SG missense mutant is a substrate for endoplasmic reticulum-associated degradation (ERAD), indicating premature degradation due to protein folding defects. In conclusion, our study underscores the utility of zebrafish in modeling sarcoglycanopathies through either gene knockout or future knock-in techniques. These novel zebrafish lines will not only enhance our understanding of the disease's pathogenic mechanisms, but will also serve as powerful tools for phenotype-based drug screening, ultimately contributing to the development of a cure for sarcoglycanopathies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping