JC polyoma virus (JCPyV), a ubiquitous polyoma virus that commonly infects people, is identified as the etiologic factor for progressive multifocal leukoencephalopathy and has been closely linked to various human cancers. Transgenic mice of CAG-loxp-Laz-loxp T antigen were established. T-antigen expression was specifically activated in gastroenterological target cells with a LacZ deletion using a cre-loxp system. Gastric poorly-differentiated carcinoma was observed in T antigen-activated mice using K19-cre (stem-like cells) and PGC-cre (chief cells), but not Atp4b-cre (parietal cells) or Capn8-cre (pit cells) mice. Spontaneous hepatocellular and colorectal cancers developed in Alb-cre (hepatocytes)/T antigen and villin-cre (intestinal cells)/T antigen transgenic mice respectively. Gastric, colorectal, and breast cancers were observed in PGC-cre/T antigen mice. Pancreatic insulinoma and ductal adenocarcinoma, gastric adenoma, and duodenal cancer were detected in Pdx1-cre/T antigen mice. Alternative splicing of T antigen mRNA occurred in all target organs of these transgenic mice. Our findings suggest that JCPyV T antigen might contribute to gastroenterological carcinogenesis with respect to cell specificity. Such spontaneous tumor models provide good tools for investigating the oncogenic roles of T antigen in cancers of the digestive system.

JC多瘤病毒（JCPyV）是一种普遍存在的多瘤病毒，通常感染人类，被确定为进行性多灶性白质脑病的病因，并与多种人类癌症密切相关。建立了CAG-loxp-Laz-loxp T抗原转基因小鼠。使用 cre-loxp 系统在具有 LacZ 缺失的胃肠道靶细胞中特异性激活 T 抗原表达。使用 K19-cre（干细胞样细胞）和 PGC-cre（主细胞）在 T 抗原激活小鼠中观察到胃癌低分化癌，但 Atp4b-cre（壁细胞）或 Capn8-cre（凹陷细胞）小鼠中未观察到胃癌低分化癌。Alb-cre（肝细胞）/T 抗原和villin-cre（肠细胞）/T 抗原转基因小鼠分别产生自发性肝细胞癌和结直肠癌。在 PGC-cre/T 抗原小鼠中观察到胃癌、结直肠癌和乳腺癌。在 Pdx1-cre/T 抗原小鼠中检测到胰腺胰岛素瘤和导管腺癌、胃腺瘤和十二指肠癌。T 抗原 mRNA 的选择性剪接发生在这些转基因小鼠的所有靶器官中。我们的研究结果表明，就细胞特异性而言，JCPyV T 抗原可能有助于胃肠道癌发生。这种自发肿瘤模型为研究 T 抗原在消化系统癌症中的致癌作用提供了良好的工具。