A rat gastrin-human gastrin chimeric transgene directs antral g
cell specific expression in transgenic mice..
Wang, Timothy C., Mark W. Babyatsky, Phillip S. Oates, Zhensheng
Zhang, Loyal Tillotson, Marybeth Chulak, Stephen J. Brand, and Emmett
V. Schmidt.
Gastrointestinal Unit, Department of Medicine, Massachusetts
General Hospital, 32 Fruit Street, Boston, MA 02114, Massachusetts
General Hospital Cancer Center, Building 149 13th Street,
Charlestown, MA 02129
APStracts 2:0020G, 1995.
Gastrin gene expression in the gastrointestinal tract is under both
developmental and spatial regulation. In the mature animal, gastrin,
an important regulator of parietal acid secretion, is expressed
primarily in G cells of the antrum. To determine whether specific
promoter elements can direct expression to the gastric antrum in vivo,
450 nucleotides of the proximal rat gastrin promoter were cloned and
used to construct a rat gastrin-human gastrin reporter chimeric
transgene which was injected into the mouse germline. Northern blot
analysis, in situ hybridization, and double-label immunocytochemistry
studies demonstrated expression of the transgene specifically in
antral G cells. Low levels of transgene expression were observed in
the ileum and colon, where immunohistochemical studies demonstrated
co-localization in PYY-expressing enteroendocrine cells. The same 450
nucleotide rat gastrin promoter, when joined to the human growth
hormone gene, did not result in antral expression. Similarly, a human
gastrin-human gastrin reporter transgene also did not achieve antral
expression, although it did express in the liver. These results
suggest that cis-acting elements present in both the basal 450
nucleotide rat gasrin promoter and the intragenic sequences of the
human gastrin gene are necessary to direct expression of a transgene
specifically to antral G cells.
Received 27 April 1994; accepted in final form 4 January 1995.
APS Manuscript Number G154-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 February 1995.