Higher proportion of intact exon 9 CFTR mRNA in nasal epithelium compared with vas deferens.
نویسندگان
چکیده
The 5-thymidine (5T) variant of the cystic fibrosis transmembrane conductance regulator (CFTR) intron 8 polypyrimidine tract (IVS8-T tract) is the most frequent CFTR gene alteration identified in men with congenital bilateral absence of vas deferens (CBAVD). This alternative splicing variant gives rise to two transcripts, one normal with exon 9 intact and the other with in-frame deletion of exon 9. That CBAVD men usually have none of the other clinical signs of classical cystic fibrosis (CF) suggests less functional CFTR is produced in the reproductive tract than in other CF-associated organs. Nasal epithelia and segments of vas deferens were obtained from healthy, previously vasectomized men who presented for vasectomy reversal. Quantitative RT-PCR was performed on these specimens, with the region of CFTR cDNA spanning exon 9 amplified. For both nasal and vasal tissues, a strong positive correlation was found between the length of the IVS8-T tract and the proportion of mRNA with exon 9 intact. In addition, within the same subject, a significantly higher level of transcripts lacking exon 9 was found in vas deferens than nasal epithelia, regardless of the IVS8-T genotype. These findings suggest that the splicing of CFTR precursor mRNA is less efficient in vasal epithelia compared with respiratory epithelia. Thus, differential splicing efficiency between the various tissues which express CFTR provides one possible explanation for the reproductive tract abnormalities observed in infertile men with CFTR gene alterations but without other clinical manifestations of CF.
منابع مشابه
Increased proportion of exon 9 alternatively spliced CFTR transcripts in vas deferens compared with nasal epithelial cells.
CFTR transcripts have been qualitatively and quantitatively analysed in nasal epithelial and vas deferens cells by means of reverse transcription PCR. Alternative splicing of exon 9, which is known to occur in nasal epithelial cells, also occurred in vas deferens cells. The extent of this alternative splicing was determined by the allele present at the Tn locus at the end of intron 8 of the CFT...
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ورودعنوان ژورنال:
- Human molecular genetics
دوره 6 12 شماره
صفحات -
تاریخ انتشار 1997