Cell-specific and developmental regulation of rabbit surfactant protein B promoter in transgenic mice.
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.
Adams
C C
CC
Department of Molecular Biology, University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708-3154, USA.
Alam
M N
MN
Starcher
B C
BC
Boggaram
V
V
D000375:Aging / Q000502:physiology*; D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D015870:Gene Expression; D008168:Lung / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000502:physiology*; D011510:Proteolipids / Q000235:genetics*; D011663:Pulmonary Surfactants / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits
D011510:Proteolipids; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D015500:Chloramphenicol O-Acetyltransferase