Summary The Preclinical Models Core assists members of the San Diego Digestive Diseases Research Center (SDDRC) in applying and phenotyping preclinical models of digestive diseases in their research. Tremendous progress in understanding the pathophysiological principles governing many of these diseases has been made by the use of animal models. The Core provides SDDRC investigators with access to a range of conventional and gnotobiotic murine models of infection and inflammation in the intestinal tract and liver, cutting-edge technologies for histological and intravital analysis, and primary human liver cells for functional studies. The Core also assists SDDRC investigators in model selection and interpretation, data acquisition from animal models, and histopathologic evaluation. The Core is directed by highly experienced investigators at the University of California San Diego (UCSD) with a deep background in studies using animals and primary human cells. The Core cooperates closely with an existing shared facility, the Microscopy and Histology Core of the La Jolla Institute for Immunology (LJI) on the UCSD campus, for cost-effective access to histological services and leverages technical services from the UCSD Animal Care Program. Past Core utilization has been excellent, as demonstrated by overall use by 61% of all Center members during the reporting period, generation and use of 2,323 gnotobiotic mice and 696 genetically engineered mice and processing of ~27,400 histological samples, leading to 67 publications over the past 4 years that acknowledge SDDRC support primarily based on Core use. Center investments contributed, on average, to 25% cost reduction for gnotobiotic mice and services, and a 43% reduction in histology costs. Building on these accomplishments, the Core will continue to provide access to a range of murine models of digestive diseases and give extensive histological and phenotyping support. In addition, member requests have led the Core to expand the model offerings to normal human liver cells isolated from rejected donor livers. Specific Core services include; 1) Tissue phenotyping by histology and live animal imaging; 2) Support for gnotobiotic animal models; 3) Access and guidance for a range of murine models of digestive diseases; 4) Access to isolated hepatocytes and non- parenchymal cells from normal human livers; and 5) Histopathological consultation and scoring. Core experts also provide individual advice and guidance on selection and interpretation of the most appropriate animal models of luminal or liver disease, train Center members and their lab personnel in gnotobiotic and other animal techniques, so they can conduct their own colonization and challenge experiments, and give regular workshops on relevant lab skills and histological approaches. Together, the models, services and protocols provided by the Preclinical Models Core will support and empower Center investigators to conduct cutting-edge research with so...