Reduced α-galactosidase A activity in zebrafish (Danio rerio) mirrors distinct features of Fabry nephropathy phenotype

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Hassan O.A. Elsaid - , University of Bergen (Autor:in)
  • Jessica Furriol - , University of Bergen (Autor:in)
  • Maria Blomqvist - , University of Gothenburg (Autor:in)
  • Mette Diswall - , University of Gothenburg (Autor:in)
  • Sabine Leh - , University of Bergen (Autor:in)
  • Naouel Gharbi - , Norwegian Research Centre (Autor:in)
  • Jan Haug Anonsen - , Norwegian Research Centre (Autor:in)
  • Janka Babickova - , University of Bergen, Comenius University (Autor:in)
  • Camilla Tøndel - , University of Bergen (Autor:in)
  • Einar Svarstad - , University of Bergen (Autor:in)
  • Hans Peter Marti - , University of Bergen (Autor:in)
  • Maximilian Krause - , Norwegian Research Centre, University of Bergen (Autor:in)

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.

Details

OriginalspracheEnglisch
Aufsatznummer100851
Seitenumfang11
FachzeitschriftMolecular Genetics and Metabolism Reports
Jahrgang31
PublikationsstatusVeröffentlicht - Juni 2022
Peer-Review-StatusJa
Extern publiziertJa

Externe IDs

WOS 000779212500006
ORCID /0000-0002-7715-1160/work/142255284

Schlagworte

Forschungsprofillinien der TU Dresden

DFG-Fachsystematik nach Fachkollegium

Fächergruppen, Lehr- und Forschungsbereiche, Fachgebiete nach Destatis

Schlagwörter

  • Fabry disease, GLA, Zebrafish, α-GAL activity, α-Galactosidase A, -Galactosidase A, &alpha, -GAL activity, Gla

Bibliotheksschlagworte