Skip to main content

From man to fish: What can Zebrafish tell us about ApoL1 nephropathy?

Publication ,  Journal Article
Olabisi, O; Al-Romaih, K; Henderson, J; Tomar, R; Drummond, I; MacRae, C; Pollak, M
Published in: Clin Nephrol

BACKGROUND: Risk variant Apolipoprotein L1 (G1/G2) are strongly associated with a spectrum of kidney disease in people of recent African descent. The mechanism of ApoL1 nephropathy is unknown. Podocytes and/or endothelial cells are the presumed target kidney cells. Given the close homology in structure and function of zebrafish (ZF) pronephros and human nephron, we studied the effect of podocyte-specific or endothelium-specific expression of ApoL1 (G0, G1, or G2) on the structure and function of ZF pronephros. METHODS: Wild type (G0) or risk variant ApoL1 (G1/G2) were expressed in podocyte-specific or endothelium-specific under podocin/Flk promoters, respectively, using Gal4-UAS system. Structural pronephric changes were studied with light and electron microscopy (EM). Proteinuria was assayed by measuring renal excretion of GFP-vitamin D binding protein. Puromycin aminonucleoside (PAN) was used as inducer of podocyte injury. RESULTS: Endothelial-specific transgenic expression of G1/G2 is associated with endothelial injury indicated by endothelial cell swelling, segmental early double contours, and loss of endothelium fenestrae. Podocyte specific expression of G1 is associated with segmental podocyte foot process effacement and irregularities relative to G0. Despite the histological changes, the expression of G1/G2 alone in podocyte or endothelium compartment is not associated with edema, proteinuria, or gross whole fish phenotype. Moreover, PAN produced equal pericardial edema in all transgenic fish as well as nontransgenic controls. CONCLUSIONS: Transgenic expression human ApoL1 (G1/G2) is associated with histologic abnormalities in ZF glomeruli but is insufficient to cause quantifiable renal dysfunction. This finding supports the necessity of a "second hit" in the pathogenesis/progression of ApoL1-associated nephropathy.

Duke Scholars

Published In

Clin Nephrol

DOI

ISSN

0301-0430

Volume

86 (2016)

Issue

13

Start / End Page

114 / 118

Location

Germany

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Vitamin D-Binding Protein
  • Vascular Endothelial Growth Factor Receptor-2
  • Urology & Nephrology
  • Transcription Factors
  • Proteinuria
  • Pronephros
  • Promoter Regions, Genetic
  • Podocytes
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Olabisi, O., Al-Romaih, K., Henderson, J., Tomar, R., Drummond, I., MacRae, C., & Pollak, M. (n.d.). From man to fish: What can Zebrafish tell us about ApoL1 nephropathy? Clin Nephrol, 86 (2016)(13), 114–118. https://doi.org/10.5414/CNP86S116
Olabisi, Opeyemi, Khaldoun Al-Romaih, Joel Henderson, Ritu Tomar, Iain Drummond, Calum MacRae, and Martin Pollak. “From man to fish: What can Zebrafish tell us about ApoL1 nephropathy?Clin Nephrol 86 (2016), no. 13 (n.d.): 114–18. https://doi.org/10.5414/CNP86S116.
Olabisi O, Al-Romaih K, Henderson J, Tomar R, Drummond I, MacRae C, et al. From man to fish: What can Zebrafish tell us about ApoL1 nephropathy? Clin Nephrol. 86 (2016)(13):114–8.
Olabisi, Opeyemi, et al. “From man to fish: What can Zebrafish tell us about ApoL1 nephropathy?Clin Nephrol, vol. 86 (2016), no. 13, pp. 114–18. Pubmed, doi:10.5414/CNP86S116.
Olabisi O, Al-Romaih K, Henderson J, Tomar R, Drummond I, MacRae C, Pollak M. From man to fish: What can Zebrafish tell us about ApoL1 nephropathy? Clin Nephrol. 86 (2016)(13):114–118.

Published In

Clin Nephrol

DOI

ISSN

0301-0430

Volume

86 (2016)

Issue

13

Start / End Page

114 / 118

Location

Germany

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Vitamin D-Binding Protein
  • Vascular Endothelial Growth Factor Receptor-2
  • Urology & Nephrology
  • Transcription Factors
  • Proteinuria
  • Pronephros
  • Promoter Regions, Genetic
  • Podocytes