| Autor: |
Ostrom, Lance, Tang, Ming-Jer, Gruss, Peter, Dressler, Gregory R. |
| Zdroj: |
Developmental Biology; March 2000, Vol. 219 Issue: 2 p250-258, 9p |
| Abstrakt: |
The murine cpkmouse develops a rapid-onset polycystic kidney disease (PKD) with many similarities to human PKD. During kidney development, the transcription factor Pax2 is required for the specification and differentiation of the renal epithelium. In humans, Pax2is also expressed in juvenile cystic kidneys where it correlates with cell proliferation. In this report, Pax2expression is demonstrated in the cystic epithelium of the mouse cpkkidneys. To assess the role of Pax2during the development of polycystic kidney disease, the progression of renal cysts was examined in cpkmutants carrying one or two alleles of Pax2.Reduced Pax2gene dosage resulted in a significant inhibition of renal cyst growth while maintaining more normal renal structures. The inhibition of cyst growth was not due to reduced proliferation of the cystic epithelium, rather to increased cell death in the Pax2heterozygotes. Increased apoptosis with reduced Pax2gene dosage was also observed in normal developing kidneys. Thus, increased cell death is an integral part of the Pax2heterozygous phenotype and may be the underlying cause of Pax gene haploinsufficiency. That the cystic epithelium requires Pax2for continued expansion underscores the embryonic nature of the renal cystic cells and may provide new insights toward growth suppression strategies. |
| Databáze: |
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