Referenced in: none

Automatically associated channels: Kir6.2 , Slo1

Title: Defining a link with autosomal-dominant polycystic kidney disease in mice with congenitally low expression of Pkd1.

Authors: Si-Tse Jiang, Yuan-Yow Chiou, Ellian Wang, Hsiu-Kuan Lin, Yuan-Ta Lin, Ying-Chih Chi, Chi-Kuang Leo Wang, Ming-Jer Tang, Hung Li

Journal, date & volume: Am. J. Pathol., 2006 Jan , 168, 205-20

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16400024

Abstract
Mouse models for autosomal-dominant polycystic kidney disease (ADPKD), derived from homozygous targeted disruption of Pkd1 gene, generally die in utero or perinatally because of systemic defects. We introduced a loxP site and a loxP-flanked mc1-neo cassette into introns 30 and 34, respectively, of the Pkd1 locus to generate a conditional, targeted mutation. Significantly, before excision of the floxed exons and mc1-neo from the targeted locus by Cre recombinase, mice homozygous for the targeted allele appeared normal at birth but developed polycystic kidney disease with a slower progression than that of Pkd-null mice. Further, the homozygotes continued to produce low levels of full-length Pkd1-encoded protein, suggesting that slight Pkd1 expression is sufficient for renal cyst formation in ADPKD. In this viable model, up-regulation of heparin-binding epidermal growth factor-like growth factor accompanied increased epidermal growth factor receptor signaling, which may be involved in abnormal proliferation of the cyst-lining epithelia. Increased apoptosis in cyst epithelia was only observed in the later period that correlated with the cyst regression. Abnormalities in Na(+)/K(+)-ATPase, aquaporin-2, and vasopressin V2 receptor expression were also identified. This mouse model may be suitable for further studies of progression and therapeutic interventions of ADPKD.