Letter abstract
Nature Genetics 39, 1018 - 1024 (2007)
Published online: 8 July 2007 | doi:10.1038/ng2072
Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis
Massimo Attanasio1,8, N Henriette Uhlenhaut2,8, Vitor H Sousa2,7, John F O'Toole1, Edgar Otto1, Katrin Anlag2, Claudia Klugmann2, Anna-Corina Treier2, Juliana Helou1, John A Sayer1, Dominik Seelow3,4, Gudrun Nürnberg3,4, Christian Becker3,4, Albert E Chudley5, Peter Nürnberg3,6, Friedhelm Hildebrandt1 & Mathias Treier2
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 genes1, 2, 3, 4 has linked its pathogenesis to primary cilia function3, 5. 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.
- Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
- Developmental Biology Unit, European Molecular Biology Laboratory, D-69117 Heidelberg, Germany.
- Cologne Center for Genomics, University of Cologne, D-50674 Cologne, Germany.
- RZPD Deutsches Ressourcenzentrum für Genomforschung GmbH, D-14059 Berlin, Germany.
- Departments of Pediatrics and Child Health, Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba R3E3P4, Canada.
- Institute for Genetics, University of Cologne, D-50674 Cologne, Germany.
- Present address: Smilow Research Center, New York University, New York, New York 10016, USA.
- These authors contributed equally to this work.
Correspondence to: Friedhelm Hildebrandt1 e-mail: fhilde@med.umich.edu
Correspondence to: Mathias Treier2 e-mail: treier@embl.de
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determinationNature Genetics Article (01 Aug 2003)
Phosphorylation by casein kinase 2 induces PACS-1 binding of nephrocystin and targeting to ciliaThe EMBO Journal Article (21 Dec 2005)
See all 19 matches for Research
