Surfactant protein C (SP-C) is a hydrophobic surfactant protein which confers surface activity on phospholipids mixtures in vitro and is a component of replacement surfactants used in the treatment of infants with RDS. We have cloned and sequenced the human SP-C gene. Transgenic mice generated with 3.7 kb of human SP-C flanking DNA directed lung-specific expression of a reporter gene (CAT). In situ hybridization localized the 3.7 SP-C-CAT transgene expression to cells of the bronchiolar and alveolar epithelium, distinct from the alveolar Type II cell-restricted expression of the endogenous SP-C gene. In order to localize regulatory elements directing the alveolar and bronchiolar patterns of SP-C expression we have subsequently generated transgenic mice with truncations and internal deletions of the original 3.7 kb SP-C DNA promoter. Transgenic mice generated with terminal deletions from the 3.7 kb SP-C down to only 1.2 or 0.6 kb SP-C DNA produced lung-specific expression. Internal deletions that retain 440 or 220 base pairs of the promoter adjacent to the SP-C promoter also elicit lung specific expression, functionally mapping the regulatory region to within 220 base pairs of the SP-C promoter. The pattern of SP-C-CAT transgene expression was detected by in situ hybridization of lungs from transgenic mice. The deletion of -1910 to -220 bp demonstrated a pattern of focal alveolar cell expression with the loss of bronchiolar expression. Deletion of the -3470 to -2390 region altered the uniform bronchiolar expression to an interspersed pattern of expression. These results suggest that distinct cis-active elements within the -1910 to -220 bp region of SP-C DNA direct the bronchiolar expression and cis-active elements within the proximal -220 bp regulate alveolar expression of SP-C and also there are functionally related subpopulations of airway epithelial cells. These same SP-C CAT transgenic lines will be used to localize developmental control elements.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account
Continue with Google
Continue with ORCiD