STUDIES IN TRANSGENIC MICE REVEAL POTENTIAL RELATIONSHIPS BETWEEN SECRETIN-PRODUCING CELLS AND OTHER ENDOCRINE CELL-TYPES

We have produced transgenic mice expressing fusion genes consisting of 1.6 kilobase pairs of the secretin gene 5' flanking region to direct the expression of human growth hormone (hGH) or simian virus 40 large T antigen to secretin-producing cells, Analysis of different mouse tis sues for hGH transcripts revealed expression in each of the major secr etin-producing tissues, namely the intestine and endocrine pancreas. M ultiple label immunohistochemistry demonstrated that the transgene was correctly directed to secretin cells in the intestinal tract, includi ng a previously unrecognized population of secretin cells in the colon of adult and developing mice, In the small intestine, subpopulations of hGH-containing cells frequently coexpressed substance P, serotonin, and cholecystokinin whereas in the colon cells expressing hGH frequen tly coexpressed glucagon, peptide YY, or neurotensin, Transgenic mice expressing large T antigen in secretin cells developed poorly differen tiated neuroendocrine tumors of the small intestine, well differentiat ed colonic tumors containing glucagon-expressing cells, and insulin-pr oducing tumors in pancreas, These studies indicate that the major cis- regulatory sequences necessary for secretin expression in enteroendocr ine cells and fetal islets are localized with 1.6 kilobase pairs of th e transcriptional start site, Coexpression of reporter transgenes with several gastrointestinal hormones suggests a potential relationships between secretin cells and other enteroendocrine cell types, as well a s pancreatic beta cells.