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- W2120428327 abstract "The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes a cAMP-activated chloride (Cl−) channel, and expression of the full length gene in vitro is sufficient to correct the Cl− conductance defect that is characteristic of cystic fibrosis (CF) epithelial cells. Alternatively spliced forms of CFTR mRNA have been identified in several tissues from normal individuals. One of the alternative transcripts, often present at high levels, results in the in-frame deletion of exon 9. Translation of this transcript would result in a CFTR protein missing the amino terminal portion of the first nucleotide binding fold (NBF). To evaluate the possible function of this form of CFTR, a cDNA representing this transcript (CFTRΔ9) was transduced into CFPAC cells, which are derived from a CF patient. CFTRΔ9 RNA was expressed in the transduced cell lines, but only immature, incompletely glycosylated protein was detectable by Western blot analysis. No increase in cAMP-activated anion permeability was detectable by 125I efflux assay or by means of the halide sensitive dye 6-methoxy-N-(3-sulfopropyl) quinolinium (SPQ). In a second assay system, in vitro synthesized mRNA representing CFTRΔD9 was injected into Xenopus oocytes, but expression of this alternatively spliced form of CFTR was not associated with the appearance of Cl− conductance. These results suggest that the protein produced by the CFTRΔ9 transcript is not properly processed and is not capable of generating Cl− conductance in response to cAMP. Whether this alternative transcript has some other function or represents ‘noise’ in the mRNA splicing mechanism remains unresolved." @default.
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- W2120428327 date "1993-01-01" @default.
- W2120428327 modified "2023-09-26" @default.
- W2120428327 title "Expression of an abundant alternatively spliced form of the cystic fibrosis transmembrane conductance regulator (CFTR) gene is not associated with a cAMP-activated chloride conductance" @default.
- W2120428327 doi "https://doi.org/10.1093/hmg/2.3.225" @default.
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