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

Frank Zaucke, Joana M. Boehnlein, Sarah Steffens, Roman S. Polishchuk, Luca Rampoldi, Andreas Fischer, Andreas Pasch, Christoph W A Boehm, Anne Baasner, Massimo Attanasio, Bernd Hoppe, Helmut Hopfer, Bodo B. Beck, John A. Sayer, Friedhelm Hildebrandt, Matthias T F Wolf

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article numberddq077
Pages (from-to)1985-1997
Number of pages13
JournalHuman Molecular Genetics
Volume19
Issue number10
DOIs
StatePublished - Feb 18 2010

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Uromodulin
Cilia
Kidney
Mutation
Cystic Kidney Diseases
Proteins
Spindle Poles
Basal Bodies
Biopsy
Kinesin
Hyperuricemia
Spindle Apparatus
Gout
Kidney Diseases
Genes
Chronic Kidney Failure
Fluorescent Antibody Technique
Cysts
Histology
Electron Microscopy

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Zaucke, F., Boehnlein, J. M., Steffens, S., Polishchuk, R. S., Rampoldi, L., Fischer, A., ... Wolf, M. T. F. (2010). Uromodulin is expressed in renal primary cilia and UMOD mutations result in decreased ciliary uromodulin expression. Human Molecular Genetics, 19(10), 1985-1997. [ddq077]. https://doi.org/10.1093/hmg/ddq077

Uromodulin is expressed in renal primary cilia and UMOD mutations result in decreased ciliary uromodulin expression. / Zaucke, Frank; Boehnlein, Joana M.; Steffens, Sarah; Polishchuk, Roman S.; Rampoldi, Luca; Fischer, Andreas; Pasch, Andreas; Boehm, Christoph W A; Baasner, Anne; Attanasio, Massimo; Hoppe, Bernd; Hopfer, Helmut; Beck, Bodo B.; Sayer, John A.; Hildebrandt, Friedhelm; Wolf, Matthias T F.

In: Human Molecular Genetics, Vol. 19, No. 10, ddq077, 18.02.2010, p. 1985-1997.

Research output: Contribution to journalArticle

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 2010, 'Uromodulin is expressed in renal primary cilia and UMOD mutations result in decreased ciliary uromodulin expression', Human Molecular Genetics, vol. 19, no. 10, ddq077, pp. 1985-1997. https://doi.org/10.1093/hmg/ddq077
Zaucke F, Boehnlein JM, Steffens S, Polishchuk RS, Rampoldi L, Fischer A et al. Uromodulin is expressed in renal primary cilia and UMOD mutations result in decreased ciliary uromodulin expression. Human Molecular Genetics. 2010 Feb 18;19(10):1985-1997. ddq077. https://doi.org/10.1093/hmg/ddq077
Zaucke, Frank ; Boehnlein, Joana M. ; Steffens, Sarah ; Polishchuk, Roman S. ; Rampoldi, Luca ; Fischer, Andreas ; Pasch, Andreas ; Boehm, Christoph W A ; Baasner, Anne ; Attanasio, Massimo ; Hoppe, Bernd ; Hopfer, Helmut ; Beck, Bodo B. ; Sayer, John A. ; Hildebrandt, Friedhelm ; Wolf, Matthias T F. / Uromodulin is expressed in renal primary cilia and UMOD mutations result in decreased ciliary uromodulin expression. In: Human Molecular Genetics. 2010 ; Vol. 19, No. 10. pp. 1985-1997.
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