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Uromodulin is expressed in renal primary cilia and UMOD mutations result in decreased ciliary uromodulin expression

Lookup NU author(s): Professor John Sayer

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Abstract

Uromodulin (UMOD) mutations are responsible for three autosomal dominant tubulo-interstitial nephropathies including medullary cystic kidney disease type 2 (MCKD2), familial juvenile hyperuricemic nephropathy and glomerulocystic kidney disease. Symptoms include renal salt wasting, hyperuricemia, gout, hypertension and end-stage renal disease. MCKD is part of the 'nephronophthisis-MCKD complex', a group of cystic kidney diseases. Both disorders have an indistinguishable histology and renal cysts are observed in either. For most genes mutated in cystic kidney disease, their proteins are expressed in the primary cilia/basal body complex. We identified seven novel UMOD mutations and were interested if UMOD protein was expressed in the primary renal cilia of human renal biopsies and if mutant UMOD would show a different expression pattern compared with that seen in control individuals. We demonstrate that UMOD is expressed in the primary cilia of renal tubules, using immunofluorescent studies in human kidney biopsy samples. The number of UMOD-positive primary cilia in UMOD patients is significantly decreased when compared with control samples. Additional immunofluorescence studies confirm ciliary expression of UMOD in cell culture. Ciliary expression of UMOD is also confirmed by electron microscopy. UMOD localization at the mitotic spindle poles and colocalization with other ciliary proteins such as nephrocystin-1 and kinesin family member 3A is demonstrated. Our data add UMOD to the group of proteins expressed in primary cilia, where mutations of the gene lead to cystic kidney disease.


Publication metadata

Author(s): Zaucke F, Boehnlein JM, Steffens S, Polishchuk RS, Rampoldi L, Fischer A, Pasch A, Boehm CWA, Baasner A, Attanasio M, Hoppe B, Hopfer H, Beck BB, Sayer JA, Hildebrandt F, Wolf MTF

Publication type: Article

Publication status: Published

Journal: Human Molecular Genetics

Year: 2010

Volume: 19

Issue: 10

Pages: 1985-1997

Print publication date: 18/02/2010

ISSN (print): 0964-6906

ISSN (electronic): 1460-2083

Publisher: Oxford University Press

URL: http://dx.doi.org/10.1093/hmg/ddq077

DOI: 10.1093/hmg/ddq077


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