1. Correction of lethal intestinal defect in a mouse model of cystic fibrosis by human CFTR
- Author
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Zhou, Lan, Dey, Chitta R., Wert, Susan E., DuVall, Michael D., Frizzell, Raymond A., and Whitsett, Jeffrey A.
- Subjects
Cystic fibrosis -- Models -- Research ,Mice -- Research -- Models ,Science and technology ,Models ,Research - Abstract
Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). A potential animal model of CF, the [CFTR.sup.-/-] mouse, has had limited utility because most mice die from intestinal obstruction during the first month of life. Human CFTR (HCFTR) was expressed in [CFTR.sup.-/-] mice under the control of the rat intestinal fatty acid-binding protein gene promoter. The mice survived and showed functional correction of ileal goblet cell and crypt cell hyperplasia and cyclic adenosine monophosphate-stimulated chloride secretion. These results support the concept that transfer of the HCFTR gene may be a useful strategy for correcting physiologic defects in patients with CF., Cystic fibrosis mice bearing a null mutation in the CFTR gene lack adenosine 3',5'-monophosphate (cAMP)--stimulated [Cl.sup.-] transport in intestinal epithelial cells, which leads to goblet cell hyperplasia, intestinal obstruction, and [...]
- Published
- 1994