Cell-specific and developmental regulation of rabbit surfactant protein B promoter in transgenic mice

Surfactant protein B (SP-B) is expressed tissue specifically in the lung an d is developmentally regulated. To identify genomic regions that control SP -B expression, we analyzed SP-B promoter activity in transgenic mice contai ning rabbit SP-B 5'-flanking DNA fragments linked to the chloramphenicol ac etyltransferase (CAT) reporter gene. Results showed that whereas the -2,176 /+39-bp fragment failed to express CAT, shorter fragments of -730/+39 and - 236/+39 bp expressed CAT tissue specifically in the lung. Further deletion of 5'-flanking DNA to -136 bp resulted in no expression of CAT. Immunostain ing demonstrated that both -730/+39- and -236/+39-bp regions expressed CAT specifically in alveolar type II and Clara cells. The -236/+39-bp region ex pressed CAT at a significantly lower level than the -730/+39-bp region. CAT expression in mice containing the -730/+39-bp region was detected in embry onic day 14 lung and attained maximum levels in day 18 lung, indicating tha t the developmental expression of CAT was similar to that of SP-B. These da ta show that the DNA elements necessary for cell type-specific expression a re located within -236/+39 bp of the SP-B gene. Additionally, these data su ggest that the -2,176/-730- and -730/-236-bp regions contain the DNA elemen ts that repress and enhance SP-B gene transcription, respectively.