1. Uromodulin is expressed in renal primary cilia and UMOD mutations result in decreased ciliary uromodulin expression
- Author
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Andreas Fischer, Christoph Boehm, Roman S. Polishchuk, Bodo B. Beck, Andreas Pasch, Helmut Hopfer, Massimo Attanasio, Friedhelm Hildebrandt, Matthias T.F. Wolf, Frank Zaucke, Sarah Steffens, Luca Rampoldi, Bernd Hoppe, John A. Sayer, Anne Baasner, Joana M. Boehnlein, Zaucke, F, Boehnlein, Jm, Steffens, S, Polishchuk, R, Rampoldi, L, Fischer, A, Pasch, A, Boehm, Cwa, Baasner, A, Attanasio, M, Hoppe, B, Hopfer, H, Beck, Bb, Sayer, Ja, Hildebrandt, F, and Wolf, Mtf
- Subjects
Tamm–Horsfall protein ,Biopsy ,030232 urology & nephrology ,Fluorescent Antibody Technique ,Kinesins ,Kidney ,Mice ,0302 clinical medicine ,Mucoproteins ,Child ,Genetics (clinical) ,Cells, Cultured ,Cystic kidney ,0303 health sciences ,medicine.diagnostic_test ,Cilium ,General Medicine ,Articles ,Middle Aged ,3. Good health ,Protein Transport ,medicine.anatomical_structure ,Renal biopsy ,Cell Division ,Adult ,medicine.medical_specialty ,Adolescent ,Blotting, Western ,Biology ,Transfection ,Antibodies ,03 medical and health sciences ,Cystic kidney disease ,Young Adult ,Internal medicine ,Uromodulin ,Genetics ,medicine ,Animals ,Humans ,Cilia ,Molecular Biology ,030304 developmental biology ,Adaptor Proteins, Signal Transducing ,Kidney metabolism ,Membrane Proteins ,medicine.disease ,Cytoskeletal Proteins ,Endocrinology ,Membrane protein ,Mutation ,biology.protein ,Mutant Proteins - 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.
- Published
- 2010
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