PUBLICATION

Knockdown of ApoL1 in Zebrafish Larvae Affects the Glomerular Filtration Barrier and the Expression of Nephrin

Authors
Kotb, A.M., Simon, O., Blumenthal, A., Vogelgesang, S., Dombrowski, F., Amann, K., Zimmermann, U., Endlich, K., Endlich, N.
ID
ZDB-PUB-160504-7
Date
2016
Source
PLoS One   11: e0153768 (Journal)
Registered Authors
Keywords
Larvae, Zebrafish, Morpholino, Edema, Dextran, Kidneys, Glomeruli, Chronic kidney disease
MeSH Terms
  • Animals
  • Apolipoproteins/deficiency*
  • Apolipoproteins/genetics*
  • Edema/metabolism
  • Endothelium/metabolism
  • Gene Expression Regulation/genetics*
  • Glomerular Filtration Barrier/metabolism*
  • Larva/genetics*
  • Larva/metabolism
  • Membrane Proteins/genetics*
  • Organ Specificity
  • Pericardium/metabolism
  • Podocytes/metabolism
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Zebrafish Proteins/deficiency*
  • Zebrafish Proteins/genetics*
PubMed
27138898 Full text @ PLoS One
Abstract
APOL1, a secreted high-density lipoprotein, is expressed in different human tissues. Genetic variants of APOL1 are described to be associated with the development of end stage renal diseases in African Americans. In human kidney, APOL1 is mainly expressed in podocytes that are responsible for proper blood filtration. Since mice do not express ApoL1, the zebrafish is an ideal model to study the role of ApoL1. Injection of morpholinos against zApoL1 into zebrafish eggs and larvae, respectively, induces severe edema indicating a leakage of the filtration barrier. This was demonstrated in zApoL1 knockdown larvae by intravascular injection of fluorescently-labeled 10- and 500-kDa dextrans and by clearance of the vitamin D-binding protein from the circulation. Immunohistochemistry and RT-PCR revealed the reduction of nephrin, a podocyte-specific protein essential for blood filtration. Coinjection of human nephrin mRNA rescued the zApoL1 knockdown induced phenotype. Reduced APOL1 and nephrin levels were also found in biopsies of patients suffering from end stage renal diseases. Our results demonstrate that zApoL1 is essential for proper blood filtration in the zebrafish glomerulus and that zApoL1 affects the expression of nephrin.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping