Header

UZH-Logo

Maintenance Infos

Moderate Nucleoporin 133 deficiency leads to glomerular damage in zebrafish


Cianciolo Cosentino, Chiara; Berto, Alessandro; Pelletier, Stéphane; Hari, Michelle; Loffing, Johannes; Neuhauss, Stephan C F; Doye, Valérie (2019). Moderate Nucleoporin 133 deficiency leads to glomerular damage in zebrafish. Scientific Reports, 9:4750.

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.

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.

Statistics

Citations

Dimensions.ai Metrics

Altmetrics

Downloads

17 downloads since deposited on 11 Apr 2019
17 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Anatomy
07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:18 March 2019
Deposited On:11 Apr 2019 14:29
Last Modified:17 Sep 2019 20:21
Publisher:Nature Publishing Group
ISSN:2045-2322
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41598-019-41202-4
PubMed ID:30894603

Download

Download PDF  'Moderate Nucleoporin 133 deficiency leads to glomerular damage in zebrafish'.
Preview
Content: Published Version
Filetype: PDF
Size: 3MB
View at publisher
Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)