PUBLICATION
Reduced α-galactosidase A activity in zebrafish (Danio rerio) mirrors distinct features of Fabry nephropathy phenotype
- Authors
- Elsaid, H.O.A., Furriol, J., Blomqvist, M., Diswall, M., Leh, S., Gharbi, N., Anonsen, J.H., Babickova, J., Tøndel, C., Svarstad, E., Marti, H.P., Krause, M.
- ID
- ZDB-PUB-220305-7
- Date
- 2022
- Source
- Molecular genetics and metabolism reports 31: 100851 (Journal)
- Registered Authors
- Krause, Maximilian, Marti, Hans-Peter
- Keywords
- Fabry disease, GLA, Zebrafish, α-GAL activity, α-Galactosidase A
- MeSH Terms
- none
- PubMed
- 35242583 Full text @ Mol Genet Metab Rep
Citation
Elsaid, H.O.A., Furriol, J., Blomqvist, M., Diswall, M., Leh, S., Gharbi, N., Anonsen, J.H., Babickova, J., Tøndel, C., Svarstad, E., Marti, H.P., Krause, M. (2022) Reduced α-galactosidase A activity in zebrafish (Danio rerio) mirrors distinct features of Fabry nephropathy phenotype. Molecular genetics and metabolism reports. 31:100851.
Abstract
Fabry disease (FD) is a rare genetic lysosomal storage disorder, resulting from partial or complete lack of alpha-galactosidase A (α-GAL) enzyme, leading to systemic accumulation of substrate glycosphingolipids with a broad range of tissue damage. Current in vivo models are laborious, expensive, and fail to adequately mirror the complex FD physiopathology. To address these issues, we developed an innovative FD model in zebrafish. Zebrafish GLA gene encoding α-GAL enzyme presents a high (>70%) homology with its human counterpart, and the corresponding protein has a similar tissue distribution, as evaluated by immunohistochemistry. Moreover, a similar enzymatic activity in different life stages could be demonstrated. By using CRISPR/Cas9 technology, we generated a mutant zebrafish with decreased GLA gene expression, and decreased expression of the specific gene product in the kidney. Mutant animals showed higher plasma creatinine levels and proteinuria. Transmission electron microscopy (TEM) studies documented an increased podocyte foot process width (FPW) in mutant, as compared to wild type zebrafish. This zebrafish model reliably mirrors distinct features of human FD and could be advantageously used for the identification of novel biomarkers and for an effective screening of innovative therapeutic approaches.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping