Moderate Nucleoporin 133 deficiency leads to glomerular damage in zebrafish

Sci Rep. 2019 Mar 18;9(1):4750. doi: 10.1038/s41598-019-41202-4.

Abstract

Although structural nuclear pore proteins (nucleoporins) are seemingly required in every cell type to assemble a functional nuclear transport machinery, mutations or deregulation of a subset of them have been associated with specific human hereditary diseases. In particular, previous genetic studies of patients with nephrotic syndrome identified mutations in Nup107 that impaired the expression or the localization of its direct partner at nuclear pores, Nup133. In the present study, we characterized the zebrafish nup133 orthologous gene and its expression pattern during larval development. Using a morpholino-mediated gene knockdown, we show that partial depletion of Nup133 in zebrafish larvae leads to the formation of kidney cysts, a phenotype that can be rescued by co-injection of wild type mRNA. Analysis of different markers for tubular and glomerular development shows that the overall kidney development is not affected by nup133 knockdown. Likewise, no gross defect in nuclear pore complex assembly was observed in these nup133 morphants. On the other hand, nup133 downregulation results in proteinuria and moderate foot process effacement, mimicking some of the abnormalities typically featured by patients with nephrotic syndrome. These data indicate that nup133 is a new gene required for proper glomerular structure and function in zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Knockdown Techniques
  • Kidney Diseases / genetics*
  • Kidney Diseases / pathology
  • Kidney Glomerulus / pathology*
  • Larva / growth & development
  • Larva / metabolism
  • Nephrotic Syndrome / etiology
  • Nuclear Pore Complex Proteins / genetics*
  • Proteinuria / etiology
  • Zebrafish
  • Zebrafish Proteins / genetics*

Substances

  • Nuclear Pore Complex Proteins
  • Zebrafish Proteins
  • nup133 protein, zebrafish