Dual gene deficient models of ApcMin/+ mouse in assessing molecular mechanisms of intestinal carcinogenesis
Dual gene deficient models of ApcMin/+ mouse in assessing molecular mechanisms of intestinal carcinogenesis
复制标题
ApcMin/小鼠双基因缺陷模型评估肠道癌发生的分子机制
DOI：
10.1016/j.biopha.2018.09.056
复制
发表时间：
2018
影响因子：
7.5
通讯作者：
Lu Wang
中科院分区：
文献类型：
--
作者：
Shuwen Yu;Yanhui Yin;Qian Wang;Lu Wang
携带大肠腺瘤性息肉病（Apc）基因失活等位基因的ApcMin/+小鼠是广泛应用的人类结直肠肿瘤发生的动物模型。这些小鼠与其他基因敲除或敲入小鼠杂交，在研究人类肠道肿瘤发生方面具有优势。肠道肿瘤的发病机制涉及多基因改变；因此，各种双基因缺失模型可以为肿瘤生物学的分子机制、肠道肿瘤发生的基因-基因相互作用以及评估预防和治疗肠癌的新策略提供新的见解。本文综述了大约100只双基因缺陷小鼠及其相关的肠道肿瘤发生和进展表型。基于Apc突变背景的双基因敲除包括炎症免疫相关基因、细胞周期相关基因、Wnt/β-catenin信号相关基因、肿瘤生长因子（TGF）信号相关基因、药物代谢相关基因、转录因子相关基因，以及部分致癌基因和肿瘤抑制基因。未来的研究应侧重于条件或诱导双或多小鼠基因敲除模型，以探讨肠道肿瘤发生的分子机制，以及潜在的药物靶点。
The ApcMin/+mouse, carrying an inactivated allele of the adenomatous polyposis coli (Apc) gene, is a widely used animal model of human colorectal tumorigenesis. While crossed with other gene knockout or knock-in mice, these mice possess advantages in investigation of human intestinal tumorigenesis. Intestinal tumor pathogenesis involves multiple gene alterations; thus, various double gene deficiency models could provide novel insights into molecular mechanisms of tumor biology, as well as gene-gene interactions involved in intestinal tumor development and assessment of novel strategies for preventing and treating intestinal cancer. This review discusses approximately 100 double gene deficient mice and their associated intestinal tumor development and progression phenotypes. The dual gene knockouts based on the Apc mutation background consist of inflammation and immune-related, cell cycle-related, Wnt/β-catenin signaling-related, tumor growth factor (TGF)-signaling-related, drug metabolism-related, and transcription factor genes, as well as some oncogenes and tumor suppressors. Future studies should focus on conditional or inducible dual or multiple mouse gene knockout models to investigate the molecular mechanisms underlying intestinal tumor development, as well as potential drug targets.