RRC ID 12152
Author Takayama H, Takagi H, Larochelle WJ, Kapur RP, Merlino G.
Title Ulcerative proctitis, rectal prolapse, and intestinal pseudo-obstruction in transgenic mice overexpressing hepatocyte growth factor/scatter factor.
Journal Lab Invest
Abstract Hepatocyte growth factor/scatter factor (HGF/SF) can stimulate growth of gastrointestinal epithelial cells in vitro; however, the physiological role of HGF/SF in the digestive tract is poorly understood. To elucidate this in vivo function, mice were analyzed in which an HGF/SF transgene was overexpressed throughout the digestive tract. Nearly a third of all HGF/SF transgenic mice in this study (28 of 87) died by 6 months of age as a result of sporadic intestinal obstruction of unknown etiology. Enteric ganglia were not overtly affected, indicating that the pathogenesis of this intestinal lesion was different from that operating in Hirschsprung's disease. Transgenic mice also exhibited a rectal inflammatory bowel disease (IBD) with a high incidence of anorectal prolapse. Expression of interleukin-2 was decreased in the transgenic colon, indicating that HGF/SF may influence regulation of the local intestinal immune system within the colon. These results suggest that HGF/SF plays an important role in the development of gastrointestinal paresis and chronic intestinal inflammation. HGF/SF transgenic mice may represent a useful model for the study of molecular mechanisms associated with a subset of IBD and intestinal pseudo-obstruction. Moreover, our data identify previously unappreciated side effects that may be encountered when using HGF/SF as a therapeutic agent.
Volume 81(3)
Pages 297-305
Published 2001-3-1
DOI 10.1038/labinvest.3780238
PMID 11310823
MeSH Animals Colitis, Ulcerative / mortality Colitis, Ulcerative / pathology* Female Gene Expression Hepatocyte Growth Factor / genetics* Humans Interleukin-2 / genetics Intestinal Pseudo-Obstruction / mortality Intestinal Pseudo-Obstruction / pathology* Intestine, Large / pathology Intestine, Large / physiology Male Mice Mice, Transgenic Proto-Oncogene Proteins c-kit / genetics Rectal Prolapse / mortality Rectal Prolapse / pathology* Survival Rate
IF 4.197
Times Cited 13
DNA material pUC kit EH1 Mouse c-kit cDNA (RDB01344)