PUBLICATION

Moderate Nucleoporin 133 deficiency leads to glomerular damage in zebrafish

Authors

Cianciolo Cosentino, C., Berto, A., Pelletier, S., Hari, M., Loffing, J., Neuhauss, S.C.F., Doye, V.

ID

ZDB-PUB-190322-5

Date

2019

Source

Scientific Reports 9: 4750 (Journal)

Registered Authors

Keywords

none

MeSH Terms

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

(all 14)

PubMed

30894603 Full text @ Sci. Rep.

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.

Genes / Markers

Marker	Marker Type	Name
cdh17	GENE	cadherin 17, LI cadherin (liver-intestine)
nup133	GENE	nucleoporin 133
pax2a	GENE	paired box 2a
wt1a	GENE	WT1 transcription factor a

Figures

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Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO2-nup133 + MO3-nup133	standard conditions	Prim-5	whole organism nup133 expression decreased amount, abnormal	Fig. 2
WT + MO2-nup133 + MO3-nup133	standard conditions	Prim-5	whole organism Ab1-nup133 labeling decreased amount, abnormal	Fig. S3
WT + MO2-nup133 + MO3-nup133	standard conditions	Long-pec	pronephric glomerulus increased size, abnormal	Fig. 5
WT + MO2-nup133 + MO3-nup133	standard conditions	Long-pec	whole organism nup133 expression decreased amount, abnormal	Fig. 2
WT + MO2-nup133 + MO3-nup133	standard conditions	Protruding-mouth	pericardium edematous, abnormal	Fig. S3
WT + MO2-nup133 + MO3-nup133	standard conditions	Protruding-mouth	pronephros cystic, abnormal	Fig. S3
WT + MO2-nup133 + MO3-nup133	standard conditions	Protruding-mouth	pronephros cystic, abnormal	Fig. 3
WT + MO2-nup133 + MO3-nup133	standard conditions	Protruding-mouth	whole organism decreased life span, abnormal	Fig. S3
WT + MO2-nup133 + MO3-nup133	standard conditions	Day 4	glomerular filtration decreased process quality, abnormal	Fig. 6
WT + MO2-nup133 + MO3-nup133	standard conditions	Day 5	pronephric capsular space pronephric podocyte morphology, abnormal	Fig. S6

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
li1Tg	Tg(wt1b:EGFP)	Transgenic Insertion

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
nup133	MO2-nup133	MRPHLNO
nup133	MO3-nup133	MRPHLNO

Fish

Fish
li1Tg
li1Tg + MO2-nup133 + MO3-nup133
WT
WT + MO2-nup133 + MO3-nup133

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Cianciolo Cosentino et al., 2019 ZDB-PUB-190322-5 PMID:30894603

Moderate Nucleoporin 133 deficiency leads to glomerular damage in zebrafish

Cianciolo Cosentino et al., 2019

ZDB-PUB-190322-5
PMID:30894603