Role of CFTR in autosomal recessive polycystic kidney disease. J Am Soc Nephrol 2001 Apr;12(4):719-725
Date
03/29/2001Pubmed ID
11274233DOI
10.1681/ASN.V124719Scopus ID
2-s2.0-0035079421 (requires institutional sign-in at Scopus site) 35 CitationsAbstract
An extensive body of in vitro data implicates epithelial chloride secretion, mediated through cystic fibrosis transmembrane conductance regulator (CFTR) protein, in generating or maintaining fluid filled cysts in MDCK cells and in human autosomal dominant polycystic kidney disease (ADPKD). In contrast, few studies have addressed the pathophysiology of fluid secretion in cyst formation and enlargement in autosomal recessive polycystic kidney disease (ARPKD). Murine models of targeted disruptions or deletions of specific genes have created opportunities to examine the role of individual gene products in normal development and/or disease pathophysiology. The creation of a murine model of CF, which lacks functional CFTR protein, provides the opportunity to determine whether CFTR activity is required for renal cyst formation in vivo. Therefore, this study sought to determine whether renal cyst formation could be prevented by genetic complementation of the BPK murine model of ARPKD with the CFTR knockout mouse. The results of this study reveal that in animals that are homozygous for the cystic gene (bpk), the lack of functional CFTR protein on the apical surface of cystic epithelium does not provide protection against cyst growth and subsequent decline in renal function. Double mutant mice (bpk -/-; cftr -/-) developed massively enlarged kidneys and died, on average, 7 d earlier than cystic, non-CF mice (bpk -/-; cftr +/+/-). This suggests fundamental differences in the mechanisms of transtubular fluid secretion in animal models of ARPKD compared with ADPKD.
Author List
Nakanishi K, Sweeney WE Jr, Macrae Dell K, Cotton CU, Avner EDAuthor
Ellis D. Avner MD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBile Duct Diseases
Cystic Fibrosis Transmembrane Conductance Regulator
Dilatation, Pathologic
Female
Kidney
Lectins
Male
Mice
Mice, Knockout
Mice, Mutant Strains
Polycystic Kidney, Autosomal Recessive
Survival Analysis
