title: A guide to histomorphological evaluation of intestinal inflammation in mouse models.
abstract: Histomorphology remains a powerful routine evaluating intestinal inflammation in animal models. Emphasizing the focus of a given animal study, histopathology can overstate differences between established models. We aimed to systematize histopathological evaluation of intestinal inflammation in mouse models facilitating inter-study comparisons. Samples of all parts of the intestinal tract from well-established mouse models of intestinal inflammation were evaluated from hematoxylin/eosin-stained sections and specific observations confirmed by subsequent immunohistochemistry. Three main categories sufficiently reflected the severity of histopathology independent of the localization and the overall extent of an inflammation: (i) quality and dimension of inflammatory cell infiltrates, (ii) epithelial changes and (iii) overall mucosal architecture. Scoring schemata were defined along specified criteria for each of the three categories. The direction of the initial hit proved crucial for the comparability of histological changes. Chemical noxes, infection with intestinal parasites or other models where the barrier was disturbed from outside, the luminal side, showed high levels of similarity and distinct differences to changes in the intestinal balance resulting from inside events like altered cytokine responses or disruption of the immune cell homeostasis. With a high degree of generalisation and maximum scores from 4-8 suitable scoring schemata accounted specific histopathological hallmarks. Truly integrating demands and experiences of gastroenterologists, mouse researchers, microbiologists and pathologists we provide an easy-to-use guideline evaluating histomorphology in mouse models of intestinal inflammation. Standard criteria and definitions facilitate classification and rating of new relevant models, allow comparison in animal studies and transfer of functional findings to comparable histopathologies in human disease.
authors.affiliation: Department of Medicine I for Gastroenterology, Infectious Disease and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin Berlin, Germany ; Research Center ImmunoSciences, Charité-Universitätsmedizin Berlin Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Erben
authors.affiliation: Pathotres Joint Practice for Pathology Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.affiliation: Cold Spring Harbor Laboratory New York, USA.
authors.forename: Katja
authors.initials: K
authors.lastname: Doerfel
authors.affiliation: Department of Medicine I for Gastroenterology, Infectious Disease and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin Berlin, Germany ; Research Center ImmunoSciences, Charité-Universitätsmedizin Berlin Berlin, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Spieckermann
authors.affiliation: Research Centre for Nutrition and Food Sciences, Biofunctionality Unit (ZIEL), Technical University Munich Freising-Weihenstephan, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Haller
authors.affiliation: Institute for Microbiology and Infectious Medicine, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin Berlin, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Heimesaat
authors.affiliation: Department of Medicine I for Gastroenterology, Infectious Disease and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zeitz
authors.affiliation: Department of Medicine I for Gastroenterology, Infectious Disease and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin Berlin, Germany ; Research Center ImmunoSciences, Charité-Universitätsmedizin Berlin Berlin, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Siegmund
authors.affiliation: Department of Medicine I for Gastroenterology, Infectious Disease and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin Berlin, Germany ; Research Center ImmunoSciences, Charité-Universitätsmedizin Berlin Berlin, Germany.
authors.forename: Anja A
authors.initials: AA
authors.lastname: Kühl
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry / Q000592:standards; D015212:Inflammatory Bowel Diseases / Q000473:pathology*; D051379:Mice
keywords: Histopathology; inflammation; inflammatory bowel disease; mouse models; scoring