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- Title
Comparison of Pkd1-targetedmutants reveals that loss of polycystin-1 causes cystogenesis andbone defects.
- Authors
Lu, Weining; Shen, Xiaohua; Pavlova, Anna; Lakkis, Montaha; Ward, ChristopherJ.; Pritchard, Lynn; Harris, PeterC.; Genest, DavidR.; Perez-Atayde, AntonioR.; ZhouTowhom correspondence ahould be addressed at: Harvard Institutes ofMedicine, Room 522, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.Tel: +1 617 525 5860; Fax: +1 617 525 5861; Email:zhou@rics.bwh.harvard.eduPresent address:Weining Lu, ..., Jing
- Abstract
A high level of polycystin-1 expression is detectedin kidneys of all patients with autosomal dominant polycystic kidneydisease (ADPKD). Mice that overexpress polycystin-1 also developrenal cysts. Whether overexpression of polycystin-1 is necessary forcyst formation is still unclear. Here, we report the generationof a targeted mouse mutant with a null mutationin Pkd1and its phenotypic characterization incomparison with the del34 mutants that carry a ‘truncationmutation’ in Pkd1. We show that null homozygotesdevelop the same, but more aggressive, renal and pancreatic cysticdisease as del34/del34. Moreover, we reportthat both homozygous mutants develop polyhydramnios, hydrops fetalis, spinabifida occulta and osteochondrodysplasia. Heterozygotes also developadult-onset pancreatic disease. We show further that del34 homozygotes continueto produce mutant polycystin-1, thereby providing a possible explanationfor increased immunoreactive polycystin-1 in ADPKD cyst epitheliain the context of the two-hit model. Our data demonstrate for thefirst time that loss of polycystin-1 leads to cyst formation anddefective skeletogenesis, and indicate that polycystin-1 is criticalin both epithelium and chondrocyte development.
- Publication
Human Molecular Genetics, 2001, Vol 10, Issue 21, p2385
- ISSN
0964-6906
- Publication type
Article