title: Complementation of null CF mice with a human CFTR YAC transgene.
abstract: We have made transgenic mice carrying a 320 kb YAC with the intact human cystic fibrosis transmembrane regulator (CFTR) gene. Mice that only express the human transgene were obtained by breeding with Cambridge null CF mice. One line has approximately two copies of the intact YAC. Mice carrying this transgene and expressing no mouse cftr appear normal and breed well, in marked contrast to the null mice, where 50% die by approximately 5 days after birth. The chloride secretory responses in these mice are as large or larger than in wild-type tissues. Expression of the transgene is highly cell type specific and matches that of the endogenous mouse gene in the crypt epithelia throughout the gut and in salivary gland tissue. However, there is no transgene expression in some tissues, such as the Brunner's glands, where it would be expected. Where there are differences between the mouse and human pattern of expression, the transgene follows the mouse pattern. We have thus defined a cloned fragment of DNA which directs physiological levels of expression in many of the specific cells where CFTR is normally expressed.
authors.affiliation: Imperial College School of Medicine at St Mary's, London, UK.
authors.forename: A L
authors.initials: AL
authors.lastname: Manson
authors.forename: A E
authors.initials: AE
authors.lastname: Trezise
authors.forename: L J
authors.initials: LJ
authors.lastname: MacVinish
authors.forename: K D
authors.initials: KD
authors.lastname: Kasschau
authors.forename: N
authors.initials: N
authors.lastname: Birchall
authors.forename: V
authors.initials: V
authors.lastname: Episkopou
authors.forename: G
authors.initials: G
authors.lastname: Vassaux
authors.forename: M J
authors.initials: MJ
authors.lastname: Evans
authors.forename: W H
authors.initials: WH
authors.lastname: Colledge
authors.forename: A W
authors.initials: AW
authors.lastname: Cuthbert
authors.forename: C
authors.initials: C
authors.lastname: Huxley
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics; D005576:Colforsin / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D004594:Electrophysiology; D005665:Furosemide; D005786:Gene Expression Regulation; D005816:Genetic Complementation Test; D006801:Humans; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010183:Pancreatic Ducts / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012469:Salivary Glands / Q000378:metabolism; D019076:Transgenes
chemical_list: C505032:CFTR protein, human; D002712:Chlorides; D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D005665:Furosemide; D002217:Carbachol