Cystic fibrosis transmembrane conductance regulator splice variants are not conserved and fail to produce chloride channels

Nat Genet. 1993 Aug;4(4):426-31. doi: 10.1038/ng0893-426.

Abstract

In the human CFTR only the rare exon 4- splice variant is conserved in mice. We have discovered two novel murine variants, exon 5- and exon 11b+. The exon 5- variant represents up to 40% of mRNA in all CFTR-expressing tissues and leaves the reading frame intact. The exon 11b+ variant inserts a novel exon between exons 11 and 12 with expression restricted to the testis. Two variants of 11b have been found and both introduce premature stop codons. When we expressed human CFTR variants lacking either exon 5 or exon 9 in HeLa cells, they failed to generate cAMP-mediated chloride transport, due to defective intracellular processing. The lack of conservation of splice variants between species and the inability of the more abundant splice variants to generate protein that is correctly processed argue against a physiological role and may simply represent aberrant splicing that is tolerated by the cell and organism.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chloride Channels / genetics*
  • Conserved Sequence
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Exons
  • Genetic Variation*
  • Humans
  • Introns
  • Membrane Proteins / genetics*
  • Mice
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Oligodeoxyribonucleotides
  • Organ Specificity
  • Polymerase Chain Reaction
  • Restriction Mapping

Substances

  • CFTR protein, human
  • Chloride Channels
  • Membrane Proteins
  • Oligodeoxyribonucleotides
  • Cystic Fibrosis Transmembrane Conductance Regulator