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.

中文翻译：

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通过肠上皮细胞中TROP2的异位表达改善EpCAM（TROP1）缺陷型小鼠中的先天簇状肠病。

TROP1（EpCAM）和TROP2是同源的细胞表面蛋白，在发育中的上皮和成年上皮细胞中广泛表达，并经常共同表达。EpCAM和TROP2归因于各种功能，但负责任的机制尚未完全表征，功能等效性尚未检查。成人肠道上皮细胞（IEC）表达高水平的EpCAM，而TROP2不表达。EpCAM缺乏会导致人类先天簇状肠病（CTE），并在小鼠中引起相应的致死性疾病。我们利用villin启动子在EpCAM缺陷小鼠的IEC中表达TROP2和EpCAM，以评估EpCAM和TROP2功能。EpCAM敲除小鼠的IEC中EpCAM或TROP2的表达阻止了CTE。TROP2拯救（T2R）小鼠比对照组小，而EpCAM拯救（EpR）小鼠没有。T2R小肠的直径和组织学观察到异常，并且Paneth和干细胞标志物减少。T2R小鼠还表现出肠系膜淋巴结肿大，对4 kDa FITC-右旋糖酐的通透性增加以及对去污剂诱导的结肠炎的敏感性增加，这与屏障功能受损相一致。对IEC类器官和球体的研究表明，T2R小鼠的干细胞功能也受到损害。我们得出的结论是，EpCAM和TROP2具有功能冗余，但它们并不等效。对IEC类器官和球体的研究表明，T2R小鼠的干细胞功能也受到损害。我们得出的结论是，EpCAM和TROP2具有功能冗余，但它们并不等效。对IEC类器官和球体的研究表明，T2R小鼠的干细胞功能也受到损害。我们得出的结论是，EpCAM和TROP2具有功能冗余，但它们并不等效。