Rab11FIP1-Deficient Mice Develop Spontaneous Inflammation and Show Increased Susceptibility to Colon Damage

We hypothesized that deficiency of Rab11-FIP1 would affect mucosal integrity in the intestine and generated global Rab11FIP1 knockout (KO) mice. Transcription signatures indicated that Rab11FIP1 deletion downregulated genes that mediate stress tolerance response, while genes mediating the response to infection were significantly upregulated, consistent with the inflammatory responses in the steady state. These findings suggest that Rab11FIP1 is important for cytoprotection mechanisms and for the maintenance of colonic mucosal integrity. Comparative gene expression profiling analysis of RNA-seq data for isolated colonic epithelial cells was compared between proximal and distal colons from Rab11FIP1KO, Rab11FIP2KO, and BL6J wild type mice.我们提出假说：Rab11-FIP1的缺失会影响肠道黏膜完整性，并构建了全身性Rab11FIP1敲除（KO）小鼠模型。转录组特征显示，Rab11FIP1缺失会下调介导应激耐受反应的基因，而介导感染应答的基因则显著上调，这与稳态下的炎症反应特征相符。上述研究结果表明，Rab11FIP1在细胞保护机制以及结肠黏膜完整性的维持中发挥重要作用。本研究针对分离得到的结肠上皮细胞的RNA测序（RNA-seq）数据开展比较基因表达谱分析，对比了Rab11FIP1KO、Rab11FIP2KO及BL6J野生型小鼠的近端结肠与远端结肠的基因表达差异。