{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T02:22:57Z","timestamp":1771726977203,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T00:00:00Z","timestamp":1596672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K07990"],"award-info":[{"award-number":["18K07990"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Intramural Research Program of the National Cancer Institute (Center for Cancer Research)","award":["\/"],"award-info":[{"award-number":["\/"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>TROP1 (EpCAM) and TROP2 are homologous cell surface proteins that are widely expressed, and often co-expressed, in developing and adult epithelia. Various functions have been ascribed to EpCAM and TROP2, but responsible mechanisms are incompletely characterized and functional equivalence has not been examined. Adult intestinal epithelial cells (IEC) express high levels of EpCAM, while TROP2 is not expressed. EpCAM deficiency causes congenital tufting enteropathy (CTE) in humans and a corresponding lethal condition in mice. We expressed TROP2 and EpCAM in the IEC of EpCAM-deficient mice utilizing a villin promoter to assess EpCAM and TROP2 function. Expression of EpCAM or TROP2 in the IEC of EpCAM knockout mice prevented CTE. TROP2 rescue (T2R) mice were smaller than controls, while EpCAM rescue (EpR) mice were not. Abnormalities were observed in the diameters and histology of T2R small intestine, and Paneth and stem cell markers were decreased. T2R mice also exhibited enlarged mesenteric lymph nodes, enhanced permeability to 4 kDa FITC-dextran and increased sensitivity to detergent-induced colitis, consistent with compromised barrier function. Studies of IEC organoids and spheroids revealed that stem cell function was also compromised in T2R mice. We conclude that EpCAM and TROP2 exhibit functional redundancy, but they are not equivalent.<\/jats:p>","DOI":"10.3390\/cells9081847","type":"journal-article","created":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T09:41:21Z","timestamp":1596706881000},"page":"1847","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Amelioration of Congenital Tufting Enteropathy in EpCAM (TROP1)-Deficient Mice via Heterotopic Expression of TROP2 in Intestinal Epithelial Cells"],"prefix":"10.3390","volume":"9","author":[{"given":"Gaku","family":"Nakato","sequence":"first","affiliation":[{"name":"Intestinal Microbiota Project, Intestinal Ecosystem Regulation Group, Kanagawa Institute of Industrial Science and Technology, Kawasaki-shi, Kanagawa 210-0821, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sohshi","family":"Morimura","sequence":"additional","affiliation":[{"name":"Department of Dermatology, International University of Health and Welfare, Narita-shi, Chiba 286-8520, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Lu","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Feng","sequence":"additional","affiliation":[{"name":"Retired from National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2923-9563","authenticated-orcid":false,"given":"Chuanjin","family":"Wu","sequence":"additional","affiliation":[{"name":"Laboratory of Immune Cell Biology, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark C.","family":"Udey","sequence":"additional","affiliation":[{"name":"Dermatology Division, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5147","DOI":"10.1073\/pnas.78.8.5147","article-title":"Human trophoblast cell-surface antigens defined by monoclonal antibodies","volume":"78","author":"Lipinski","year":"1981","journal-title":"Proc. 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