The long term goal of this proposal is to study the genetic regulation of development and differentiation in the lung. This proposal will investigate a cell specific marker protein, the 10 kD Clara Cell Specific Protein (CCSP) in order to identify the elements required for cell specific gene expression in the lung. This protein is specific to the Clara cells, a pivotal cell in the development of the pulmonary epithelium. The investigation will begin by analysing the developmental pattern of expression of this gene in mice. The elements controlling the expression of this gene will be located using gene transfer to the murine genome. The precise control elements regulating CCSP gene expression will be identified by using a Clara cell derived clonal cell line to dissect the cis elements required for cell.specific gene expression. This cell line will then he used to identify the transcription factors involved in CCSP gene expression. The elements identified as important for the cell specific expression of the CCSP gene will be verified by testing their ability to direct a reporter gene to the Clara cells of the lungs of transgenic mice. This developmental and molecular analysis of gene expression in the lung will allow future research to identify the genetic basis for pulmonary disease. This research will lead to the generation of animal models for lung disease and will provide the tools needed to alleviate lung disease via gene therapy.
