Antisense oligodeoxynucleotide to the cystic fibrosis gene inhibits anion transport in normal cultured sweat duct cells

Journal Article · Sun Sep 01 04:00:00 EDT 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.17.7759· OSTI ID:5823078

Sorscher, E J; Kirk, K L; Weaver, M L; Jilling, T; Blalock, J E; LeBoeuf, R D ^[1]

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1. Univ of Alabama, Birmingham (United States)

The authors have tested the hypothesis that the cystic fibrosis (CF) gene product, called the CF transmembrane conductance regulator (CFTR), mediates anion transport in normal human sweat duct cells. Sweat duct cells in primary culture were treated with oligodeoxynucleotides that were antisense to the CFTR gene transcript in order to block the expression of the wild-type CFTR. Anion transport in CFTR transcript antisense-treated cells was then assessed with a halide-specific dye, 6-methoxy-N-(3-sulfopropryl)quinolinium, and fluorescent digital imaging microscopy to monitor halide influx and efflux from single sweat duct cells. Antisense oligodeoxynucleotide treatment for 24 hr virtually abolished Cl{sup {minus}} transport in sweat duct cells compared with untreated cells or control cells treated with sense oligodeoxynucleotides. Br{sup {minus}} uptake into sweat duct cells was also blocked after a 24-hr CFTR transcript antisense treatments, but not after treatments for only 4 hr. Lower concentrations of antisense oligodeoxynucleotides were less effective at inhibiting Cl{sup {minus}} transport. These results indicate that oligodeoxynucleotides that are antisense to CFTR transcript inhibit sweat duct Cl{sup {minus}} permeability in both a time-dependent and dose-dependent manner. This approach provides evidence that inhibition of the expression of the wild-type CFTR gene in a normal, untransfected epithelial cell results in an inhibition of Cl{sup {minus}} permeability.

• OSTI ID: 5823078
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:17; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
AROMATICS
AZAARENES
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CHLORIDES
CHLORINE COMPOUNDS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DISEASES
DNA SEQUENCING
ETIOLOGY
FIBROSIS
GENES
HALIDES
HALOGEN COMPOUNDS
HEREDITARY DISEASES
HETEROCYCLIC COMPOUNDS
ISOTOPES
LIGHT NUCLEI
MEMBRANE TRANSPORT
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
OLIGONUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATHOLOGICAL CHANGES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PYRIDINES
QUINOLINES
RADIOISOTOPES
SOMATIC CELLS
STRUCTURAL CHEMICAL ANALYSIS