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
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
Figures
Figure Gallery (5 images)
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Expression
Gene Antibody Fish Conditions Stage Qualifier Anatomy Assay Figure
glaAb1-glaAB/TUstandard conditionsAdultIHC
glaAb1-glaAB/TUstandard conditionsAdultIHC
glaAb1-glaAB/TUstandard conditionsAdultIHC
glaAb1-glaAB/TUstandard conditionsAdultIHC
glaAb1-glaglahuh1/huh1 (AB/TU)standard conditionsAdultNot DetectedIHC
glaAb1-glaglahuh1/huh1 (AB/TU)standard conditionsAdultNot DetectedIHC
1 - 6 of 6
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Phenotype
Fish Conditions Stage Phenotype Figure
glahuh1/huh1 (AB/TU)standard conditionsAdult
glahuh1/huh1 (AB/TU)standard conditionsAdult
glahuh1/huh1 (AB/TU)standard conditionsAdult
glahuh1/huh1 (AB/TU)standard conditionsAdult
glahuh1/huh1 (AB/TU)standard conditionsAdult
glahuh1/huh1 (AB/TU)standard conditionsAdult
glahuh1/huh1 (AB/TU)standard conditionsAdult
glahuh1/huh1 (AB/TU)standard conditionsAdult
1 - 8 of 8
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
huh1
    		Insertion
    1 - 1 of 1
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    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    glaCRISPR1-glaCRISPR
    1 - 1 of 1
    Show
    Fish
    Fish
    AB/TU
    glahuh1/huh1 (AB/TU)
    1 - 2 of 2
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    Antibodies
    Name Type Antigen Genes Isotypes Host Organism
    Ab1-glapolyclonalRabbit
    1 - 1 of 1
    Show
    Orthology
    No data available
    Engineered Foreign Genes
    No data available
    Mapping
    No data available
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    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.