Intestinal phenotype in mice overexpressing a heparin-binding EGF-like growth factor transgene in enterocytes.
OBJECTIVE
Heparin-binding EGF-like growth factor (HB-EGF) protects the intestine from damage in animals. Future clinical trials of HB-EGF may involve administration of repeated doses of HB-EGF. Since HB-EGF activates EGF receptors which have been implicated in tumor development, we examined the effects of HB-EGF overexpression in the intestine.


METHODS
We generated transgenic (TG) mice in which the human HB-EGF gene is driven by the villin promoter to overexpress HB-EGF along the crypt-villous axis from the duodenum to the colon.


RESULTS
HB-EGF TG mice have increased enterocyte proliferation balanced by increased enterocyte apoptosis. Despite prolonged overexpression of HB-EGF, no evidence of intestinal hyperplasia or tumor formation occurs. Although HB-EGF TG mice have no significant phenotypic alterations under basal conditions, they have increased resistance to intestinal injury.


CONCLUSIONS
Prolonged intestinal HB-EGF overexpression results in no significant phenotypic alterations under basal conditions, but confers protection against intestinal injury.
Chen
Chun-Liang
CL
Department of Pediatric Surgery, The Research Institute at Nationwide Children's Hospital, Center for Perinatal Research, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH, USA.
Mehta
Veela B
VB
Zhang
Hong-Yi
HY
Wu
Dana
D
Otabor
Iyore
I
Radulescu
Andrei
A
El-Assal
Osama N
ON
Feng
Jiexiong
J
Chen
Yan
Y
Besner
Gail E
GE
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000293:injuries; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic; D019076:Transgenes / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation
C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; C026615:villin