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Am J Physiol Gastrointest Liver Physiol 277: G533-G540, 1999;
0193-1857/99 $5.00
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Vol. 277, Issue 3, G533-G540, September 1999

Intestinal overexpression of EGF in transgenic mice enhances adaptation after small bowel resection

Christopher R. Erwin, Michael A. Helmrath, Cathy E. Shin, Richard A. Falcone Jr., Lawrence E. Stern, and Brad W. Warner

Department of Surgery, Division of Pediatric Surgery, Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229-3039

The effect of direct intestinal overexpression of epidermal growth factor (EGF) on postresection adaptation has been investigated by the production of transgenic mouse lines. A murine pro-EGF cDNA construct was produced, and expression of the EGF construct was targeted to the small intestine with the use of the rat intestinal fatty acid-binding protein promoter. An approximately twofold increase in intestinal EGF mRNA and protein was detected in heterozygous mice. No changes in serum EGF levels were noted. Except for a slightly shortened small intestine, no other abnormal phenotype was observed. Intestinal adaptation (increases in body weight, DNA, protein content, villus height, and crypt depth) was markedly enhanced after a 50% proximal small bowel resection in transgenic mice compared with nontransgenic littermates. This transgenic mouse model permits the study of intestinal adaptation and other effects of EGF in the small intestine in a more physiological and directed manner than has been previously possible. These results endorse a direct autocrine/paracrine mechanism for EGF on enterocytes as a means to enhance adaptation.

intestinal resection; intestine development; short gut; RT-PCR; ribonuclease protection assay; epidermal growth factor


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