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Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis

Lookup NU author(s): Professor John Sayer

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Abstract

Nephronophthisis (NPHP), an autosomal recessive kidney disease, is the most frequent genetic cause of end-stage renal failure in the first three decades of life. Positional cloning of the six known NPHP genes has linked its pathogenesis to primary cilia function. Here we identify mutation of GLIS2 as causing an NPHP-like phenotype in humans and mice, using positional cloning and mouse transgenics, respectively. Kidneys of Glis2 mutant mice show severe renal atrophy and fibrosis starting at 8 weeks of age. Differential gene expression studies on Glis2 mutant kidneys demonstrate that genes promoting epithelial-to-mesenchymal transition and fibrosis are upregulated in the absence of Glis2. Thus, we identify Glis2 as a transcription factor mutated in NPHP and demonstrate its essential role for the maintenance of renal tissue architecture through prevention of apoptosis and fibrosis.


Publication metadata

Author(s): Attanasio M, Uhlenhaut NH, Sousa VH, O'Toole JF, Otto E, Anlag K, Klugmann C, Treier AC, Helou J, Sayer JA, Seelow D, Nürnberg G, Becker C, Chudley AE, Nürnberg P, Hildebrandt F, Treier M

Publication type: Letter

Publication status: Published

Journal: Nature Genetics

Year: 2007

Volume: 39

Issue: 8

Pages: 1018-1024

ISSN (print): 1061-4036

ISSN (electronic): 1546-1718

URL: http://dx.doi.org/10.1038/ng2072

DOI: 10.1038/ng2072

PubMed id: 17618285


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