title: Skipping of exon 9 of human CFTR in YAC-transgenic mice.
abstract: Exon 9 of the human gene CFTR is skipped in some mRNA transcripts in human tissues. The level of skipping correlates with the number of TG's and T's in the 5' splice acceptor of exon 9. Poorly spliced alleles are associated with mild cystic fibrosis related phenotypes. Here we describe transgenic mice carrying a yeast artificial chromosome (YAC) with the intact human gene CFTR. When the YAC carries 10 TG's and 7 T's at the splice acceptor, there is about 50% skipping of exon 9 in most tissues, whereas 12 TG's and 5 T's give about 90% skipping. The level of skipping is quite uniform over many tissues, except the testis, in which there is a much higher level of correct splicing. These mice confirm that the TG(m)T(n) polymorphism has an effect on splicing and should be valuable for studying this phenomenon.
authors.affiliation: Faculty of Medicine, Imperial College School of Science, Technology and Medicine, London, SW7 2AZ, UK.
authors.forename: A
authors.initials: A
authors.lastname: Manson
authors.forename: C
authors.initials: C
authors.lastname: Huxley
mesh_terms: D000483:Alleles; D000818:Animals; D002460:Cell Line; D018244:Chromosomes, Artificial, Yeast; D003550:Cystic Fibrosis / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004064:Digestive System / Q000378:metabolism; D005091:Exons; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D011110:Polymorphism, Genetic; D022821:RNA Splice Sites; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D019076:Transgenes
chemical_list: C505032:CFTR protein, human; D022821:RNA Splice Sites; D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator