Sequence of the rat surfactant protein a gene and functional
mapping of its upstream region.
Smith, Candyce I., Elizabeth Rosenberg, Samuel R. Reisher, Feng Li,
Paul Kefalides, Aron B. Fisher, and Sheldon I. Feinstein.
Institute for Environmental Medicine and Departments of Genetics
and Physiology, University of Pennsylvania School of Medicine,
Philadelphia, PA 19104-6068 and Deborah Research Institute, 1 Trenton
Road, Browns Mills, NJ 08015
APStracts 2:0099L, 1995.
Surfactant protein A (SP-A) is the major pulmonary surfactant protein.
We have isolated a rat SP-A genomic clone and determined the sequence
from 2.9 kilobases upstream of the transcriptional start through the
termination of translation. The exon-intron structure of the rat gene
has been determined and compared with the mouse, rabbit and human
genes. We have localized the major transcriptional start site in
adult rat lung to nucleotide 30 downstream from the start of the TATA
box. Functional mapping indicates that a DNA fragment containing 163
nucleotides upstream of the transcriptional start (-163) can function
as a promoter of transcription of a reporter gene in both lung and
non-lung derived cell lines. However, the function of this element is
weaker in cells of non-lung origin. DNA elements located between
-2902 and -163 silence the promoter activity in both lung and non-lung
cells. Since the SP-A gene promoter region exhibits limited tissue
-specificity, the results suggest the existence of other DNA elements
which overcome the silencer and confer further lung specificity.
Received 28 March 1994; accepted in final form 30 May 1995.
APS Manuscript Number L95-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 July 1995.