PUBLICATION

Gene Expression Analysis in gla-Mutant Zebrafish Reveals Enhanced Ca2+ Signaling Similar to Fabry Disease

Authors
Elsaid, H.O.A., Tjeldnes, H., Rivedal, M., Serre, C., Eikrem, Ø., Svarstad, E., Tøndel, C., Marti, H.P., Furriol, J., Babickova, J.
ID
ZDB-PUB-230109-14
Date
2022
Source
International Journal of Molecular Sciences   24(1): (Journal)
Registered Authors
Keywords
Fabry disease, alpha-galactosidase A, calcium signaling, cardiac involvement, gla, oxidative stress, zebrafish
MeSH Terms
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Fabry Disease*/metabolism
  • Animals
  • alpha-Galactosidase/genetics
  • Signal Transduction
  • Mutation
  • Gene Expression Profiling
(all 8)
PubMed
36613802 Full text @ Int. J. Mol. Sci.
Abstract
Fabry disease (FD) is an X-linked inborn metabolic disorder due to partial or complete lysosomal α-galactosidase A deficiency. FD is characterized by progressive renal insufficiency and cardio- and cerebrovascular involvement. Restricted access on Gb3-independent tissue injury experimental models has limited the understanding of FD pathophysiology and delayed the development of new therapies. Accumulating glycosphingolipids, mainly Gb3 and lysoGb3, are Fabry specific markers used in clinical follow up. However, recent studies suggest there is a need for additional markers to monitor FD clinical course or response to treatment. We used a gla-knockout zebrafish (ZF) to investigate alternative biomarkers in Gb3-free-conditions. RNA sequencing was used to identify transcriptomic signatures in kidney tissues discriminating gla-mutant (M) from wild type (WT) ZF. Gene Ontology (GO) and KEGG pathways analysis showed upregulation of immune system activation and downregulation of oxidative phosphorylation pathways in kidneys from M ZF. In addition, upregulation of the Ca2+ signaling pathway was also detectable in M ZF kidneys. Importantly, disruption of mitochondrial and lysosome-related pathways observed in M ZF was validated by immunohistochemistry. Thus, this ZF model expands the pathophysiological understanding of FD, the Gb3-independent effects of gla mutations could be used to explore new therapeutic targets for FD.
Genes / Markers
Figures
Figure Gallery (4 images)
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Expression
No data available
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
huh1
    Insertion
    1 - 1 of 1
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    Human Disease / Model
    Human Disease Fish Conditions Evidence
    Fabry diseaseglahuh1/huh1standard conditionsTAS
    1 - 1 of 1
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    Sequence Targeting Reagents
    No data available
    Fish
    1 - 2 of 2
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    Antibodies
    Name Type Antigen Genes Isotypes Host Organism
    Ab1-idh3polyclonal
      IgGRabbit
      Ab2-ctsbmonoclonal
        IgG1Mouse
        1 - 2 of 2
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        Orthology
        No data available
        Engineered Foreign Genes
        No data available
        Mapping
        No data available