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目的 构建并验证一种与临床散发性结直肠癌类似且同时表达KrasLSL-G12D/-和Smad4loxp/loxp的双转基因小鼠模型.方法 将Krastm4Tyj/J小鼠与Smad4tm2.1Cxd/J小鼠转换遗传背景后进行杂交建系,通过聚合酶链式反应技术鉴定子代小鼠基因型,获得基因型为KrasLSL-G12D/-+Smad4loxp/loxp的双转基因小鼠模型.通过向双转基因模型小鼠的肠黏膜下注射LentivirusCre-IRES-Luciferase,在IVIS系统下观察并统计双转基因模型小鼠的成瘤情况,对其瘤变组织进行取样并行苏木精-伊红染色法染色,以验证双转基因模型小鼠的成瘤能力.结果 经培育筛选获得了能够同时表达KrasLSL-G12D/-和Smad4loxp/loxp的双转基因小鼠模型;通过构建的病毒载体利用Cre重组酶成功感染并诱导小鼠肠上皮细胞突变而形成癌灶.结论 本研究构建的KrasLSL-G12D/-+Smad4loxp/loxp双转基因模型小鼠的结肠上皮细胞能在Cre重组酶作用下诱导癌变,模拟了人类散发性结直肠癌的病理过程.“,”Objective To construct and verify a genetically engineered mouse model which is similar to clinical sporadic colorectal cancer and simultaneously expresses KrasLSL-G12D/-and Smad4loxp/loxpgenes. Methods The Krastm4Tyj/J mouse and Smad4tm2.1Cxd/J mouse were transformed into the genetic background, and the genotypes of the offspring mice were identified by the PCR to obtain the mice expressed simultaneously KrasLSL-G12D/-and Smad4loxp/loxpgenes. The LentivirusCre-IRES-Luciferasewas injected into the submucosa of the model mice and the tumorigenicity was observed under the IVIS system. The tumor tissues of the model mice were sampled and the HE staining was used to verify the tumorigenicity of the model mice. Results The genetically engineered mouse model which could simultaneously express KrasLSL-G12D/-and Smad4loxp/loxpgenes was obtained by the breeding and selection. The mouse intestinal epithelial cell carcinogenesis was successfully induced by the viral vector containing Cre recombinase. Conclusion Mouse model expressed simultaneously KrasLSL-G12D/-and Smad4loxp/loxpgenes is capable of sporadic tumorigenicity by Cre recombinase and could simulate pathological process of human sporadic colorectal cancer.