Conditional mutation of Pkd2 causes cystogenesis and upregulates beta-catenin.

Kim I, Ding T, Fu Y, Li C, Cui L, Li A, Lian P, Liang D, Wang DW, Guo C, Ma J, Zhao P, Coffey RJ, Zhan Q, Wu G
J Am Soc Nephrol. 2009 20 (12): 2556-69

PMID: 19939939 · PMCID: PMC2794231 · DOI:10.1681/ASN.2009030271

Loss of polycystin-2 (PC2) in mice (Pkd2(-/-)) results in total body edema, focal hemorrhage, structural cardiac defects, abnormal left-right axis, hepatorenal and pancreatic cysts, and embryonic lethality. The molecular mechanisms by which loss of PC2 leads to these phenotypes remain unknown. We generated a model to allow targeted Pkd2 inactivation using the Cre-loxP system. Global inactivation of Pkd2 produced a phenotype identical to Pkd2(-/-) mice with undetectable PC2 protein and perinatal lethality. Using various Cre mouse lines, we found that kidney, pancreas, or time-specific deletion of Pkd2 led to cyst formation. In addition, we developed an immortalized renal collecting duct cell line with inactive Pkd2; these cells had aberrant cell-cell contact, ciliogenesis, and tubulomorphogenesis. They also significantly upregulated beta-catenin, axin2, and cMyc. Our results suggest that loss of PC2 disrupts normal behavior of renal epithelial cells through dysregulation of beta-catenin-dependent signaling, revealing a potential role for this signaling pathway in PC2-associated ADPKD.

MeSH Terms (23)

Animals Apoptosis beta Catenin Cell Line Cell Proliferation Cysts Disease Models, Animal Female Kidney Tubules, Collecting Liver Diseases Male Mice Mice, Congenic Mice, Inbred C57BL Mice, Knockout Mutation Pancreatic Diseases Phenotype Polycystic Kidney, Autosomal Dominant Pregnancy Signal Transduction TRPP Cation Channels Up-Regulation

Connections (2)

This publication is referenced by other Labnodes entities: