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

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Item Type:	Letter
Title:	Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis
Creators Name:	Attanasio, M., Uhlenhaut, N.H., Sousa, V.H., O'Toole, J.F., Otto, E., Anlag, K., Klugmann, C., Treier, A.C., Helou, J., Sayer, J.A., Seelow, D., Nürnberg, G., Becker, C., Chudley, A.E., Nürnberg, P., Hildebrandt, F. and Treier, M.
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.
Keywords:	Apoptosis, Cell Line, Fibrosis, Kidney, Kidney Diseases, Kruppel-Like Transcription Factors, Pedigree, Animals, Dogs, Mice
Source:	Nature Genetics
ISSN:	1061-4036
Publisher:	Nature Publishing Group
Volume:	39
Number:	8
Page Range:	1018-1024
Date:	August 2007
Official Publication:	https://doi.org/10.1038/ng2072
PubMed:	View item in PubMed

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