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

Journal Article · Sun Sep 01 00:00:00 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), Vol. 88:17; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

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