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

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 th e use of the rat intestinal fatty acid-binding protein promoter. An approxi mately 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 observe d. Intestinal adaptation (increases in body weight, DNA, protein content, v illus height, and crypt depth) was markedly enhanced after a 50% proximal s mall bowel resection in transgenic mice compared with nontransgenic litterm ates. This transgenic mouse model permits the study of intestinal adaptatio n and other effects of EGF in the small intestine in a more physiological a nd directed manner than has been previously possible. These results endorse a direct autocrine/paracrine mechanism for EGF on enterocytes as a means t o enhance adaptation.