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.