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Characterization of mutations located in exon 18 of the CFTR gene
Author(s) -
Vankeerberghen Anne,
Wei Lin,
Teng Hui,
Jaspers Martine,
Cassiman Jean-Jacques,
Nilius Bernd,
Cuppens Harry
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)01042-4
Subject(s) - cystic fibrosis transmembrane conductance regulator , xenopus , chloride channel , transmembrane domain , mutation , transmembrane protein , exon , microbiology and biotechnology , chemistry , mutant , missense mutation , point mutation , amino acid , gating , biology , gene , biophysics , biochemistry , receptor
In order to get a better insight into the function of amino acid residues located in the second transmembrane domain of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, all exon 18 mutations found in cystic fibrosis (CF) patients were characterized at the protein and at the electrophysiological level. Of the different mutations present in transmembrane helix 12 (M1137V, M1137R, I1139V and ΔM1140), and the intracytoplasmic loop connecting TM12 and NBD2 (D1152H and D1154G), only M1137R interfered with the proper maturation of the protein. Permeability studies performed after injection of the different wild‐type and mutant cRNAs in Xenopus laevis oocytes indicated that the mutations did not alter the permeability sequence of the CFTR channels. The whole cell cAMP activated chloride currents, however, were significantly reduced for M1137V, I1139V, D1152H and D1154G and close to zero for ΔM1140, indicating that these mutations interfere with the proper gating of the chloride channels.