Conditional expression of fibroblast growth factor-7 in the developing and mature lung. J Biol Chem 2000 Apr 21;275(16):11858-64
Date
04/15/2000Pubmed ID
10766812DOI
10.1074/jbc.275.16.11858Scopus ID
2-s2.0-0034697322 (requires institutional sign-in at Scopus site) 284 CitationsAbstract
Effects of fibroblast growth factor-7 (FGF-7) on lung morphogenesis, respiratory epithelial cell differentiation, and proliferation were assessed in transgenic mice in which the human FGF-7 cDNA was controlled by a conditional promoter under the direction of regulatory elements from either the human surfactant protein-C (SP-C) or rat Clara cell secretory protein (ccsp) genes. Expression of FGF-7 was induced in respiratory epithelial cells of the fetal lung by administration of doxycycline to the dam. Prenatally, doxycycline induced FGF-7 mRNA in respiratory epithelial cells in both Sp-c and Ccsp transgenic lines, increasing lung size and causing cystadenomatoid malformation. Postnatally, mice bearing both Ccsp-rtta and (Teto)(7)-cmv-fgf-7 transgenes survived, and lung morphology was normal. Induction of FGF-7 expression by doxycycline in the Ccsp-rtta x (Teto)(7)-cmv-fgf-7 mice caused marked epithelial cell proliferation, adenomatous hyperplasia, and pulmonary infiltration with mononuclear cells. Epithelial cell hyperplasia caused by FGF-7 was largely resolved after removal of doxycycline. Surfactant proteins, TTF-1, and aquaporin 5 expression were conditionally induced by doxycycline. The Sp-c-rtta and Ccsp-rtta activator mice provide models in which expression is conditionally controlled in respiratory epithelial cells in the developing and mature lung, altering lung morphogenesis, differentiation, and proliferation.
Author List
Tichelaar JW, Lu W, Whitsett JAMESH terms used to index this publication - Major topics in bold
AnimalsAquaporin 5
Aquaporins
Doxycycline
Enzyme Inhibitors
Epithelial Cells
Fibroblast Growth Factor 10
Fibroblast Growth Factor 7
Fibroblast Growth Factors
Gene Expression Regulation, Developmental
Growth Substances
Humans
In Situ Hybridization
Lung
Membrane Proteins
Mice
Mice, Transgenic
Nuclear Proteins
Phospholipases A
Proteins
Proteolipids
Pulmonary Surfactants
Rats
Thyroid Nuclear Factor 1
Transcription Factors
Transgenes
Uteroglobin
