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 de velopmental 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 elem ents can direct expression to the gastric antrum in vivo, 450 nucleoti des of the proximal rat gastrin promoter were cloned and used to const ruct a rat gastrin-human gastrin reporter chimeric transgene, which wa s injected into the mouse germ line. Northern blot analysis, in situ h ybridization, and double-label immunocytochemistry studies demonstrate d expression of the transgene specifically in antral G cells. Low leve ls of transgene expression were observed in the ileum and colon, where immunohistochemical studies demonstrated colocalization in enteroendo crine cells expressing peptide YY. The same 450-nucleotide rat gastrin promoter, when joined to the human growth hormone gene, did not resul t in antral expression. Similarly, a human gastrin-human gastrin repor ter transgene also did not achieve antral expression, although it did express in the liver. These results suggest that cis-acting elements p resent in both the basal 450-nucleotide rat gastrin promoter and the i ntragenic sequences of the human gastrin gene are necessary to direct expression of a transgene specifically to antral G cells.