Human surfactant protein B promoter in transgenic mice: temporal, spatial, and stimulus-responsive regulation

Surfactant protein B (SP-B) is a developmentally and hormonally regulated lung protein that is required for normal surfactant function. We generated transgenic mice carrying the human SP-B promoter (-1,039/+431 bp) linked to chloramphenicol acetyltransferase (CAT). CAT activity was high in lung and...

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Bibliographic Details
Published in:American journal of physiology. Lung cellular and molecular physiology 2002-03, Vol.282 (3), p.L394-L404
Main Authors: Strayer, Marlene, Savani, Rashmin C, Gonzales, Linda W, Zaman, Aisha, Cui, Zheng, Veszelovszky, Edina, Wood, Emily, Ho, Ye-Shih, Ballard, Philip L
Format: Article
Language:English
Subjects:
Aging - physiology
Animals
Animals, Newborn - growth & development
Animals, Newborn - physiology
Chloramphenicol O-Acetyltransferase - genetics
Culture Techniques
Fetus - physiology
Gene Expression Regulation, Developmental
Humans
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Transgenic - genetics
Peptide Fragments - genetics
Promoter Regions, Genetic - physiology
Proteolipids - genetics
Pulmonary Surfactants - genetics
Time Factors
Tissue Distribution
Transgenes - physiology
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Summary:Surfactant protein B (SP-B) is a developmentally and hormonally regulated lung protein that is required for normal surfactant function. We generated transgenic mice carrying the human SP-B promoter (-1,039/+431 bp) linked to chloramphenicol acetyltransferase (CAT). CAT activity was high in lung and immunoreactive protein localized to alveolar type II and bronchiolar epithelial cells. In addition, thyroid, trachea, and intestine demonstrated CAT activity, and each of these tissues also expressed low levels of SP-B mRNA. Developmental expression of CAT activity and SP-B mRNA in fetal lung were similar and both increased during explant culture. SP-B mRNA but not CAT activity decreased during culture of adult lung, and both were reduced by transforming growth factor (TGF)-beta(1). Treatment of adult mice with intratracheal bleomycin caused similar time-dependent decreases in lung SP-B mRNA and CAT activity. These findings indicate that the human SP-B promoter fragment directs tissue- and lung cell-specific transgene expression and contains cis-acting elements involved in regulated expression during development, fetal lung explant culture, and responsiveness to TGF-beta and bleomycin-induced lung injury.
ISSN:1040-0605
1522-1504
DOI:10.1152/ajplung.00188.2001