Effects of cystic fibrosis and congenital bilateral absence of the vas deferens-associated mutations on cystic fibrosis transmembrane conductance regulator-mediated regulation of separate channels

John E. Mickle, Michał J. Milewski, Milan Macek, Garry R. Cutting

Research output: Contribution to journalArticle


The protein defective in cystic fibrosis (CF), the CF transmembrane- conductance regulator (CFTR), functions as an epithelial chloride channel and as a regulator of separate ion channels. Although the consequences that disease-causing mutations have on the chloride-channel function have been studied extensively, little is known about the effects that mutations have on the regulatory function. To address this issue, we transiently expressed CFTR-bearing mutations associated with CF or its milder phenotype, congenital bilateral absence of the vas deferens, and determined whether mutant CFTR could regulate outwardly rectifying chloride channels (ORCCs). CFTR bearing a CF-associated mutation in the first nucleotide-binding domain (NBD1), ΔF508, functioned as a chloride channel but did not regulate ORCCs. However, CFTR bearing disease-associated mutations in other domains retained both functions, regardless of the associated phenotype. Thus, a relationship between loss of CFTR regulatory function and disease severity is evident for NBD1, a region of CFTR that appears important for regulation of separate channels.

Original languageEnglish (US)
Pages (from-to)1485-1495
Number of pages11
JournalAmerican journal of human genetics
Issue number5
StatePublished - Jan 1 2000


ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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