ABSTRACT
The transgenic mouse is being actively applied to the study of lung morphogenesis and repair providing the ability to assess the function of regulatory molecules, cell matrix, and cell-cell interactions in vivo (1). In the mouse lung, morphogenesis begins on day 9 postconception as evagination of the foregut endoderm into the splanchnic mesenchyme. Thereafter, epithelial cells of the lung invade the mesenchyme, undergo branching morphogenesis and form the bronchi, bronchioles, and terminal airspaces. Underlying mesenchymal cells must also proliferate and differentiate to form the underlying stromal tissues, including cartilage, pulmonary vessels and supporting smooth muscle, capillaries, and other complex structures characteristic of the mature lung. Postnatally, these structures provide stable conducting airways and gas-exchange areas, protected by complex host defenses that keep the postnatal lung free of invading organisms. Although in vitro systems have been useful in the analysis of lung cell differentiation and gene expression, the application of transgenic mice to add or mutate genes in the developing lung in vivo has become useful in defining mechanisms that determine lung morphogenesis and repair. In the present chapter, we will discuss findings from experiments with transgenic mouse models used to study lung morphogene-
912 Whitsett and Korfhagen
sis and repair, focusing on fibroblast growth factor-7 (FGF-7), transforming growth factor-α (TGF-α), and their receptors.
