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Am J Physiol Gastrointest Liver Physiol 276: G666-G676, 1999;
0193-1857/99 $5.00
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Vol. 276, Issue 3, G666-G676, March 1999

Goblet cell-specific expression mediated by the MUC2 mucin gene promoter in the intestine of transgenic mice

James R. Gum Jr.1,2, James W. Hicks3, Anne-Marie Gillespie4, Elaine J. Carlson4, Lazlo Kömüves5, Satyajit Karnik1, Joe C. Hong3, Charles J. Epstein4, and Young S. Kim1,3

1 Gastrointestinal Research Laboratory, Department of Veterans Affairs Medical Center, San Francisco 94121; and Departments of 2 Anatomy, 3 Medicine, 4 Pediatrics, and 5 Dermatology, University of California at San Francisco, California 94143

The regulation of MUC2, a major goblet cell mucin gene, was examined by constructing transgenic mice containing bases -2864 to +17 of the human MUC2 5'-flanking region fused into the 5'-untranslated region of a human growth hormone (hGH) reporter gene. Four of eight transgenic lines expressed reporter. hGH message expression was highest in the distal small intestine, with only one line expressing comparable levels in the colon. This contrasts with endogenous MUC2 expression, which is expressed at its highest levels in the colon. Immunohistochemical analysis indicated that goblet cell-specific expression of reporter begins deep in the crypts, as does endogenous MUC2 gene expression. These results indicate that the MUC2 5'-flanking sequence contains elements sufficient for the appropriate expression of MUC2 in small intestinal goblet cells. Conversely, elements located outside this region appear necessary for efficient colonic expression, implying that the two tissues utilize different regulatory elements. Thus many, but not all, of the elements necessary for MUC2 gene regulation reside between bases -2864 and +17 of the 5'-flanking region.

differentiation; gene expression; granular goblet cells; colon; human growth hormone reporter


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