Early development of polycystic kidney disease in transgenic mice expressing an activated mutant of the beta-catenin gene

Citation
S. Saadi-kheddouci et al., Early development of polycystic kidney disease in transgenic mice expressing an activated mutant of the beta-catenin gene, ONCOGENE, 20(42), 2001, pp. 5972-5981
Citations number
46
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ONCOGENE
ISSN journal
09509232 → ACNP
Volume
20
Issue
42
Year of publication
2001
Pages
5972 - 5981
Database
ISI
SICI code
0950-9232(20010920)20:42<5972:EDOPKD>2.0.ZU;2-G
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is common and is a maj or cause of renal failure. Although the genetics of ADPKD are well known an d have led to the discovery of polycystins, a new protein family, the patho genesis of the disease remains largely unknown. Recent studies have indicat ed that the beta -catenin signaling pathway is one of the targets of the tr ansduction pathway controlled by the polycystins. We have generated transge nic mice that overproduce an oncogenic form of beta -catenin in the epithel ial cells of the kidney. These mice developed severe polycystic lesions soo n after birth that affected the glomeruli, proximal, distal tubules and col lecting ducts. The phenotype of these mice mimicked the human ADPKD phenoty pe. Cyst formation was associated with an increase in cell proliferation an d apoptosis. The cell proliferation and apoptotic indexes was increased 4-5 -fold and 3-4-fold, respectively, in cystic tubules of the transgenic mice compared to that of littermate controls. Our findings provide experimental genetic evidence that activation of the Wnt/beta -catenin signaling pathway causes polycystic kidney disease and support the view that dysregulation o f the Wnt/beta -catenin signaling is involved in its pathogenesis.