AJP - Lung Cellular and Molecular Physiology, Vol 267, Issue 5 489-L497, Copyright © 1994 by American Physiological Society
Transgenic models for study of pulmonary development and disease
S. W. Glasser, T. R. Korfhagen, S. E. Wert and J. A. Whitsett
Children's Hospital Medical Center, Division of Pulmonary Biology, Cincinnati, Ohio 45229-3039.
This review summarizes progress in the application of transgenic mouse
technology to the study of lung development and disease. Since advances in
molecular genetics have greatly facilitated the isolation of cDNA and
genes, our ability to readily assess roles of both normal and mutated genes
in transgenic mouse in vivo represents a major advance, bridging molecular
biology and whole animal physiology. Strategies have been developed in
which lung epithelial cell promoter elements are used to drive normal or
mutated genes into specific subsets of respiratory epithelial cells in the
lungs of developing and mature transgenic mice. These mice have been used
to elucidate the cis-acting elements controlling lung epithelial cell gene
expression, to discern the role of specific polypeptides in lung
morphogenesis and tumorigenesis, and to create animal models of pulmonary
disease. The ability to mutate genes at their precise chromosomal locations
through gene targeting in embryonic stem cells has lead to the production
of animal models of lung diseases such as cystic fibrosis. Both gene
insertion and gene targeting create permanent mouse lines that pass the
modified gene to their progeny, providing animals for the study of the
pathogenesis and treatment of pulmonary disorders.
