A rat gastrin-human gastrin chimeric transgene directs antral G cell-specific expression in transgenic mice.
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 germ line. 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 colocalization in enteroendocrine cells expressing peptide YY. 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 gastrin promoter and the intragenic sequences of the human gastrin gene are necessary to direct expression of a transgene specifically to antral G cells.
Wang
T C
TC
Department of Medicine, Massachusetts General Hospital, Boston 02114, USA.
Babyatsky
M W
MW
Oates
P S
PS
Zhang
Z
Z
Tillotson
L
L
Chulak
M
M
Brand
S J
SJ
Schmidt
E V
EV
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D005755:Gastrins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D005768:Gastrointestinal Hormones / Q000096:biosynthesis; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010452:Peptide Biosynthesis; D019894:Peptide YY; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011706:Pyloric Antrum / Q000166:cytology / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000096:biosynthesis; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D013270:Stomach / Q000166:cytology
D017931:DNA Primers; D005755:Gastrins; D005768:Gastrointestinal Hormones; D011993:Recombinant Fusion Proteins; D019894:Peptide YY