Expression of a calmodulin inhibitor peptide in progenitor alveolar type ii cells disrupts lung development. Wang, Jiahong, Bego[tilde]na Campos, Marcia A. Kaetzel, and John R. Dedman. University of Cincinnati, Molecular and Cellular Physiology, 231 Bethesda Avenue, P.O. Box 670576, Cincinnati, OH 45267-0576
APStracts 3:0057L, 1996.
Calmodulin (CaM) is a major intracellular Ca2+ mediator protein involved in cell growth and differentiation. In order to evaluate calmodulin function in lung, it was necessary to construct a gene which encodes a high affinity calmodulin binding peptide, since chemically synthesized calmodulin inhibitors lack binding and targeting specificity. This calmodulin inhibitor peptide gene was targeted to type II epithelial cells in transgenic mice using the human surfactant protein C promoter. Neutralization of calmodulin function in progenitor type II epithelial pneumocytes alters epithelial cell growth and differentiation which prevents branching morphogenesis of the bronchial tree. Newborn transgenic animals have undeveloped lungs. This study indicates that type II lung epithelial cells require functional CaM for proliferation and development. The targeting of specific inhibitor peptides to a single lung cell type is an approach to evaluate the role of calmodulin, the ubiquitous calcium dependent regulator protein, in lung development and disease. 

Received 18 December 1995; accepted in final form 5 April 1996.
APS Manuscript Number L370-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96