{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T12:11:09Z","timestamp":1780488669783,"version":"3.54.1"},"reference-count":36,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2000,5,1]]},"abstract":"<jats:p>We used transgenic mice to identify cis-active regions of the human pulmonary surfactant protein C ( SP-C) gene that impart tissue- and cell-specific expression in vivo in the lung. Approximately 3.7 kb of genomic SP-C DNA upstream of the transcription start site was sufficient to direct chloramphenicol acetyltransferase ( CAT) reporter gene expression specifically in bronchiolar and alveolar epithelial cells of the lung. To further define cis-active regulatory elements that mediate cell-specific expression, we tested deletions of the parental 3.7-kb human SP-C sequence in transgenic mice. Tissue CAT assays of mice generated with truncations or overlapping internal deletions of the 3.7-kb construct functionally map alveolar cell-specific regulatory elements to within \u2212215 bp of the SP-C promoter. Analysis of SP-C promoter deletions demonstrate that sequences between \u22123.7 kb and \u22121.9 kb contain enhancer sequences that stimulate SP-C transgene expression. In situ hybridization studies demonstrate that deletion of the \u22121,910- to \u2212215-bp region abolishes the ectopic bronchiolar expression seen with the original 3.7-kb SP-C promoter construct. Comparison of sequences from \u2212215 to +1 bp identified consensus binding sites for the homeodomain transcription factor thyroid transcription factor-1 (TTF-1). Cotransfection assays of the human 3.7-kb SP-C or \u22121,910- to \u2212215-bp SP-C deletion construct with a TTF-1 expression plasmid demonstrates that TTF-1 transactivates the human SP-C gene. These results suggest that the TTF-1 cis-active sites are important in directing cell-specific expression of the SP-C gene in vivo.<\/jats:p>","DOI":"10.1152\/ajplung.2000.278.5.l933","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T00:34:27Z","timestamp":1514075667000},"page":"L933-L945","source":"Crossref","is-referenced-by-count":40,"title":["Human<i>SP-C<\/i>gene sequences that confer lung epithelium-specific expression in transgenic mice"],"prefix":"10.1152","volume":"278","author":[{"given":"Stephan W.","family":"Glasser","sequence":"first","affiliation":[{"name":"Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Burhans","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 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