| Nephronophthisis: disease mechanisms of a ciliopathy. | |
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MedLine Citation:
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PMID: 19118152 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Nephronophthisis (NPHP), a recessive cystic kidney disease, is the most frequent genetic cause of end-stage kidney disease in children and young adults. Positional cloning of nine genes (NPHP1 through 9) and functional characterization of their encoded proteins (nephrocystins) have contributed to a unifying theory that defines cystic kidney diseases as "ciliopathies." The theory is based on the finding that all proteins mutated in cystic kidney diseases of humans or animal models are expressed in primary cilia or centrosomes of renal epithelial cells. Primary cilia are sensory organelles that connect mechanosensory, visual, and other stimuli to mechanisms of epithelial cell polarity and cell-cycle control. Mutations in NPHP genes cause defects in signaling mechanisms that involve the noncanonical Wnt signaling pathway and the sonic hedgehog signaling pathway, resulting in defects of planar cell polarity and tissue maintenance. The ciliary theory explains the multiple organ involvement in NPHP, which includes retinal degeneration, cerebellar hypoplasia, liver fibrosis, situs inversus, and mental retardation. Positional cloning of dozens of unknown genes that cause NPHP will elucidate further signaling mechanisms involved. Nephrocystins are highly conserved in evolution, thereby allowing the use of animal models to develop future therapeutic approaches. |
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Authors:
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Friedhelm Hildebrandt; Massimo Attanasio; Edgar Otto |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review Date: 2008-12-31 |
Journal Detail:
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Title: Journal of the American Society of Nephrology : JASN Volume: 20 ISSN: 1533-3450 ISO Abbreviation: J. Am. Soc. Nephrol. Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2009-01-08 Completed Date: 2009-01-23 Revised Date: 2011-01-11 |
Medline Journal Info:
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Nlm Unique ID: 9013836 Medline TA: J Am Soc Nephrol Country: United States |
Other Details:
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Languages: eng Pagination: 23-35 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, Howard Hughes Medical Institute, University of Michigan Health System, 8220C MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5646, USA. fhilde@umich.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Signal Transducing
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genetics Calmodulin-Binding Proteins / genetics Cell Polarity Cilia / pathology* Humans Kidney Diseases, Cystic / etiology*, pathology Kinesin / genetics Kruppel-Like Transcription Factors / physiology Liver Cirrhosis / etiology, genetics Membrane Proteins / genetics Proteins / genetics Retinal Degeneration / etiology, genetics Situs Inversus / etiology, genetics Transcription Factors / physiology |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK068306-07/DK/NIDDK NIH HHS; R01-DK064614/DK/NIDDK NIH HHS; R01-DK68306/DK/NIDDK NIH HHS; R01-DK69274/DK/NIDDK NIH HHS; //Howard Hughes Medical Institute; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Signal Transducing; 0/Calmodulin-Binding Proteins; 0/GLIS2 protein, human; 0/INVS protein, human; 0/IQCB1 protein, human; 0/Kruppel-Like Transcription Factors; 0/Membrane Proteins; 0/NPHP1 protein, human; 0/NPHP4 protein, human; 0/Proteins; 0/Transcription Factors; EC 3.6.1.-/Kinesin; EC 3.6.1.-/nephrocystin-3, human |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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