| First Author | Lu W | Year | 2001 |
| Journal | Hum Mol Genet | Volume | 10 |
| Issue | 21 | Pages | 2385-96 |
| PubMed ID | 11689485 | Mgi Jnum | J:72627 |
| Mgi Id | MGI:2153323 | Doi | 10.1093/hmg/10.21.2385 |
| Citation | Lu W, et al. (2001) Comparison of Pkd1-targeted mutants reveals that loss of polycystin-1 causes cystogenesis and bone defects. Hum Mol Genet 10(21):2385-96 |
| abstractText | A high level of polycystin-1 expression is detected in kidneys of all patients with autosomal dominant polycystic kidney disease (ADPKD). Mice that overexpress polycystin-1 also develop renal cysts. Whether overexpression of polycystin-1 is necessary for cyst formation is still unclear. Here, we report the generation of a targeted mouse mutant with a null mutation in Pkd1 and its phenotypic characterization in comparison with the del34 mutants that carry a 'truncation mutation' in Pkd1. We show that null homozygotes develop the same, but more aggressive, renal and pancreatic cystic disease as del34/del34. Moreover, we report that both homozygous mutants develop polyhydramnios, hydrops fetalis, spina bifida occulta and osteochondrodysplasia. Heterozygotes also develop adult-onset pancreatic disease. We show further that del34 homozygotes continue to produce mutant polycystin-1, thereby providing a possible explanation for increased immunoreactive polycystin-1 in ADPKD cyst epithelia in the context of the two-hit model. Our data demonstrate for the first time that loss of polycystin-1 leads to cyst formation and defective skeletogenesis, and indicate that polycystin-1 is critical in both epithelium and chondrocyte development. |
