title: Early morbidity encountered in the dietary-related mouse model of Barrett's esophagus: a question of zinc?
abstract: Recently, a mouse model for Barrett's esophagus based on a zinc-deficient diet supplemented with deoxycholic bile acids has been published. The aim of this study was to attempt to reproduce these data and extend them by employing genetically modified mice and intraperitoneal iron supplementation. The study design encompassed six experimental groups (wild type, Apc-mutant and Smad4-mutant mice, with or without iron injections), with all animals fed with the zinc-deficient diet supplemented with deoxycholic bile acids. All treatments were started at 3-5 weeks of age (the majority [78%] at 5 weeks). Animals were scheduled for euthanasia at two distinct time points, namely at 3 and 6 months of age. All mice showed signs of considerable distress already 4 weeks after the start of the modified diets, and had to be euthanized before the first evaluation time point (mean age 9.3 weeks, range 5-15 weeks). No differences were observed between wild type and genetically modified mice, or between animals with or without iron supplementation. On histological examination, we could not detect any lesions (Barrett's esophagus-like or tumors) other than esophagitis. In the currently presented experimental settings, we were not able to reproduce the mouse model according to which Barrett's-like lesions could be detected in animals fed with the zinc-deficient diet supplemented with deoxycholic bile acids.
authors.affiliation: Department of Surgery,Pathology, andGastroenterology and Hepatology, Erasmus MC, Rotterdam, andDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: B A
authors.initials: BA
authors.lastname: Grotenhuis
authors.affiliation: Department of Surgery,Pathology, andGastroenterology and Hepatology, Erasmus MC, Rotterdam, andDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: P F
authors.initials: PF
authors.lastname: Franken
authors.affiliation: Department of Surgery,Pathology, andGastroenterology and Hepatology, Erasmus MC, Rotterdam, andDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: W J C
authors.initials: WJ
authors.lastname: Swinkels
authors.affiliation: Department of Surgery,Pathology, andGastroenterology and Hepatology, Erasmus MC, Rotterdam, andDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Boonstra
authors.affiliation: Department of Surgery,Pathology, andGastroenterology and Hepatology, Erasmus MC, Rotterdam, andDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: van der Valk
authors.affiliation: Department of Surgery,Pathology, andGastroenterology and Hepatology, Erasmus MC, Rotterdam, andDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: J J B
authors.initials: JJ
authors.lastname: van Lanschot
authors.affiliation: Department of Surgery,Pathology, andGastroenterology and Hepatology, Erasmus MC, Rotterdam, andDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Fodde
mesh_terms: D000818:Animals; D001471:Barrett Esophagus / Q000139:chemically induced* / Q000473:pathology; D002756:Cholagogues and Choleretics / Q000008:administration & dosage*; D003840:Deoxycholic Acid / Q000008:administration & dosage*; D004032:Diet / Q000009:adverse effects; D019587:Dietary Supplements / Q000009:adverse effects*; D004195:Disease Models, Animal; D004941:Esophagitis / Q000139:chemically induced / Q000473:pathology; D007501:Iron / Q000008:administration & dosage; D051379:Mice; D008817:Mice, Mutant Strains; D015203:Reproducibility of Results; D051901:Smad4 Protein / Q000235:genetics; D014131:Trace Elements / Q000008:administration & dosage / Q000172:deficiency*; D015032:Zinc / Q000172:deficiency*
chemical_list: D002756:Cholagogues and Choleretics; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D014131:Trace Elements; D003840:Deoxycholic Acid; D007501:Iron; D015032:Zinc