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01-02-2005 | Original Article

Exfoliated human proximal tubular cells: a model of cystinosis and Fanconi syndrome

Authors: Guido F. Laube, Mushfequr R. Haq, William G. van’t Hoff

Published in: Pediatric Nephrology | Issue 2/2005

Abstract

The renal Fanconi syndrome (FS) is characterised by generalised proximal tubular dysfunction. Cystinosis is the most common genetic cause of the FS and results from defective function of cystinosin, due to mutations of the CTNS gene leading to intralysosomal cystine accumulation. Despite these advances in our understanding of the molecular basis of cystinosis, the mechanisms of proximal tubular cell (PTC) dysfunction are still unknown. We have further characterised an in vitro model of cultured cells exfoliated in patients’ urine. We cultured cells from 9 cystinosis children, 4 children with Lowe syndrome and 8 controls. PTC phenotype and homogeneity were studied by lectin staining, immunocytochemistry (using ZO-1 as an epithelial marker) and enzyme cytochemistry (using γ-glutamyltransferase as a PTC marker). All cultured cells showed PTC phenotype. Cystinosin was stained using anti-cystinosin antibody and co-localised to the lysosomes with LAMP-2 antibody. Additionally, we have demonstrated significantly elevated intracellular cystine levels in cystinotic cell lines (13.8±2.3 nmol 1/2 cystine/mg protein, P <0.001) compared with controls. We believe this in vitro model will allow further investigation of cystinosis and other types of the FS.

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Title: Exfoliated human proximal tubular cells: a model of cystinosis and Fanconi syndrome
Authors: Guido F. Laube
Mushfequr R. Haq
William G. van’t Hoff
Publication date: 01-02-2005
Publisher: Springer-Verlag
Published in: Pediatric Nephrology / Issue 2/2005
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-004-1703-x

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Exfoliated human proximal tubular cells: a model of cystinosis and Fanconi syndrome

Abstract

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