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Am J Physiol Lung Cell Mol Physiol 280: L724-L731, 2001;
1040-0605/01 $5.00
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Vol. 280, Issue 4, L724-L731, April 2001

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

Constantin C. Adams1,*, M. Nurul Alam1,*, Barry C. Starcher2, and Vijayakumar Boggaram1

Departments of 1 Molecular Biology and 2 Biochemistry, University of Texas Health Science Center at Tyler, Tyler, Texas 75708-3154

Surfactant protein B (SP-B) is expressed tissue specifically in the lung and is developmentally regulated. To identify genomic regions that control SP-B expression, we analyzed SP-B promoter activity in transgenic mice containing rabbit SP-B 5'-flanking DNA fragments linked to the chloramphenicol acetyltransferase (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. Immunostaining 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 expressed 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 embryonic day 14 lung and attained maximum levels in day 18 lung, indicating that the developmental expression of CAT was similar to that of SP-B. These data show that the DNA elements necessary for cell type-specific expression are located within -236/+39 bp of the SP-B gene. Additionally, these data suggest that the -2,176/-730- and -730/-236-bp regions contain the DNA elements that repress and enhance SP-B gene transcription, respectively.

gene regulation; transcription; type II cell; Clara cell; respiratory distress syndrome

* C. C. Adams and M. N. Alam contributed equally to this work.




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