TY - JOUR
T1 - Human surfactant protein B promoter in transgenic mice
T2 - Temporal, spatial, and stimulus-responsive regulation
AU - Strayer, Marlene
AU - Savani, Rashmin C.
AU - Gonzales, Linda W.
AU - Zaman, Aisha
AU - Cui, Zheng
AU - Veszelovszky, Edina
AU - Wood, Emily
AU - Ho, Ye Shih
AU - Ballard, Philip L.
PY - 2002
Y1 - 2002
N2 - 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 epithehal 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)-β1. 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-β and bleomycin-induced lung injury.
AB - 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 epithehal 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)-β1. 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-β and bleomycin-induced lung injury.
KW - Bleomycin lung injury
KW - Dexamethasone
KW - Lung development
KW - Lung explant culture
KW - Transforming growth factor-β
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U2 - 10.1152/ajplung.00188.2001
DO - 10.1152/ajplung.00188.2001
M3 - Article
C2 - 11839532
AN - SCOPUS:0036081114
SN - 1040-0605
VL - 282
SP - L394-L404
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 3 26-3
ER -