V. Mak et al., HIGHER PROPORTION OF INTACT EXON-9 CFTR MESSENGER-RNA IN NASAL EPITHELIUM COMPARED WITH VAS-DEFERENS, Human molecular genetics, 6(12), 1997, pp. 2099-2107
The 5-thymidine (5T) variant of the cystic fibrosis transmembrane cond
uctance regulator (CFTR) intron 8 polypyrimidine tract (IVS8-T tract)
is the most frequent CFTR gene alteration identified in men with conge
nital bilateral absence of vas deferens (CBAVD), This alternative spli
cing Variant gives rise to two transcripts, one normal with exon 9 int
act and the other with in-frame deletion of exon 9, That CBAVD men usu
ally have none of the other clinical signs of classical cystic fibrosi
s (CF) suggests less functional CFTR is produced in the reproductive t
ract than in other CF-associated organs, Nasal epithelia and segments
of vas deferens were obtained from healthy, previously vasectomized me
n who presented for vasectomy reversal. Quantitative RT-PCR was perfor
med on these specimens, with the region of CFTR cDNA spanning exon 9 a
mplified, For both nasal and vasal tissues, a strong positive correlat
ion was found between the length of the IVS8-T tract and the proportio
n 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 les
s efficient in vasal epithelia compared with respiratory epithelia, Th
us, differential splicing efficiency between the various tissues which
express CFTR provides one possible explanation for the reproductive t
ract abnormalities observed in infertile men with CFTR gene alteration
s but without other clinical manifestations of CF.