Role of CFTR in autosomal recessive polycystic kidney disease.

Abstract

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.

• Authors: Koichi Nakanishi, William E Sweeney Jr, Katherine Macrae Dell, Calvin U Cotton, Ellis D Avner
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 12 Issue 4 Pg. 719-725 (Apr 2001) ISSN: 1046-6673 [Print] United States
• PMID: 11274233 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Lectins
• Cystic Fibrosis Transmembrane Conductance Regulator

Topics

• Animals
• Bile Duct Diseases (pathology)
• Cystic Fibrosis Transmembrane Conductance Regulator (genetics, physiology)
• Dilatation, Pathologic (pathology)
• Female
• Kidney (physiopathology)
• Lectins (metabolism)
• Male
• Mice
• Mice, Knockout (genetics)
• Mice, Mutant Strains (genetics)
• Polycystic Kidney, Autosomal Recessive (genetics, pathology, physiopathology)
• Survival Analysis