The murine SP-C promoter directs type II cell-specific expression in transgenic mice

Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio Submitted 6 July 2004 ; accepted in final form 24 November 2004 Genomic DNA from the mouse pulmonary surfactant protein C (SP-C) gene was analyzed in transgenic mice to identify DNA essential for alveolar type II cell-specific expression. SP-C promoter constructs extending either 13 or 4.8 kb upstream of the transcription start site directed lung-specific expression of the bacterial chloramphenicol acetyl transferase (CAT) reporter gene. In situ hybridization analysis demonstrated alveolar cell-specific expression in the lungs of adult transgenic mice, and the pattern of 4.8 SP-C-CAT expression during development paralleled that of the endogenous SP-C gene. With the use of deletion constructs, lung-specific, low-level CAT activity was detected in tissue assays of SP-C-CAT transgenic mice retaining 318 bp of the promoter. In transient and stable cell transfection experiments, the 4.8-kb SP-C promoter was 90-fold more active as a stably integrated gene. These findings indicate that 1 ) the 4.8-kb SP-C promoter is sufficient to direct cell-specific and developmental expression, 2 ) an enhancer essential for lung-specific expression maps to the proximal 318-bp promoter, and 3 ) the activity of the 4.8-kb SP-C promoter construct is highly dependent on its chromatin environment. surfactant protein C; type II cells Address for reprint requests and other correspondence: S. W. Glasser, Cincinnati Children's Hospital Medical Center, Div. of Pulmonary Biology, 3333 Burnet Ave., Cincinnati, OH 45229-3039 (E-mail: steve.glasser{at}cchmc.org