Correction of Lethal Intestinal Defect in a Mouse Model of Cystic Fibrosis by Human CFTR

• Published in: Science (American Association for the Advancement of Science) Vol. 266; no. 5191; pp. 1705 - 1708
• Main Authors: Zhou, Lan, Dey, Chitta R., Wert, Susan E., DuVall, Michael D., Frizzell, Raymond A., Whitsett, Jeffrey A.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 09-12-1994; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Animals; Base Sequence; Biological and medical sciences; Carrier Proteins - genetics; Chlorides - metabolism; Colforsin - pharmacology; Colon; Colon - chemistry; Colon - pathology; Complementary DNA; Crypts; Cystic fibrosis; Cystic Fibrosis - genetics; Cystic Fibrosis - metabolism; Cystic Fibrosis - pathology; Cystic Fibrosis - therapy; Cystic Fibrosis Transmembrane Conductance Regulator; Disease Models, Animal; Epithelial cells; Fatty Acid-Binding Protein 7; Fatty Acid-Binding Proteins; Feedback (Response); Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression; Genes; Genetic Therapy; House mouse; Humans; Ileum; Intestinal Mucosa - chemistry; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Intestine, Small - chemistry; Intestine, Small - pathology; Intestines; Jejunum; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Membrane Proteins - analysis; Membrane Proteins - genetics; Membrane Proteins - physiology; Messenger RNA; Mice; Mice as laboratory animals; Mice, Transgenic; Molecular Sequence Data; Neoplasm Proteins; Nerve Tissue Proteins; Other diseases. Semiology; Promoter Regions, Genetic; Rats; Recombinant Proteins - biosynthesis; RNA, Messenger - analysis; RNA, Messenger - genetics; Rodents; Transgenic animals; Tumor Suppressor Proteins; Animal model; Heterologous system; Pathophysiology; Respiratory disease; Rodentia; Transgenic animal; Cystic fibrosis; Gene expression; Genetic disease; Vertebrata; Mammalia; Mouse; Digestive diseases; Gene therapy; Pancreatic disease
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.7527588

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$^{-/-}$ 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$^{-/-}$ 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.