title: Intestinal phenotype in mice overexpressing a heparin-binding EGF-like growth factor transgene in enterocytes.
abstract: 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.
authors: 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.
authors: Chun-Liang
authors: CL
authors: Chen
authors: Veela B
authors: VB
authors: Mehta
authors: Hong-Yi
authors: HY
authors: Zhang
authors: Dana
authors: D
authors: Wu
authors: Iyore
authors: I
authors: Otabor
authors: Andrei
authors: A
authors: Radulescu
authors: Osama N
authors: ON
authors: El-Assal
authors: Jiexiong
authors: J
authors: Feng
authors: Yan
authors: Y
authors: Chen
authors: Gail E
authors: GE
authors: Besner
mesh_terms: 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
chemical_list: 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