Phenotypic consequences of lung-specific inducible expression of FGF-3

Members of the fibroblast growth factor (FGF) family play a critical role i n embryonic lung development and adult lung physiology. The in vivo investi gation of the role FGFs play in the adult lung has been hampered because th e constitutive pulmonary expression of these factors often has deleterious effects and frequently results in neonatal lethality, To circumvent these s hortcomings, we expressed FGF-3 in the lungs under the control of the proge sterone antagonist-responsive binary transgenic system. Four binary transge nic lines were obtained that showed ligand-dependent induction of FGF-3 wit h induced levels of FGF-3 expression dependent on the levels of expression of the GLp65 regulator as well as the dose of the progesterone antagonist, RU486, administered. FGF-3 expression in the adult mouse lung resulted in t wo phenotypes depending on the levels of induction of FGF-3. Low levels of FGF-3 expression resulted in massive free alveolar macrophage infiltration. High levels of FGF-3 expression resulted in diffuse alveolar type II cell hyperplasia, Both phenotypes were reversible after the withdrawal of RU486. This system will be a valuable means of investigating the diverse roles of FGFs in the adult lung.