EXPRESSION OF A CALMODULIN INHIBITOR PEPTIDE IN PROGENITOR ALVEOLAR TYPE-II CELLS DISRUPTS LUNG DEVELOPMENT

Calmodulin (CaM) is a major intracellular Ca2+ mediator protein involv ed in cell growth and differentiation. To evaluate calmodulin function in lung, it was necessary to construct a gene that encodes a high-aff inity calmodulin binding peptide, since chemically synthesized calmodu lin inhibitors lack binding and targeting specificity. This calmodulin inhibitor peptide gene was targeted to type II epithelial cells in tr ansgenic mice using the human surfactant protein C promoter. Neutraliz ation of calmodulin function in progenitor type II epithelial pneumocy tes alters epithelial cell growth and differentiation, which prevents branching morphogenesis of the bronchial tree. Newborn transgenic anim als have undeveloped lungs. This study indicates that type II lung epi thelial cells require functional CaM for proliferation and development . The targeting of specific inhibitor peptides to a single lung cell t ype is an approach to evaluate the role of calmodulin, the ubiquitous calcium-dependent regulator protein, in lung development and disease.