非肥胖性糖尿病小鼠在1型糖尿病发病过程中的基因表达谱改变

摘要

目的：用基因表达谱芯片检测非肥胖性糖尿病（non‐obese diabetic ，NOD）小鼠在1型糖尿病（T1DM ）发病过程中的基因表达。方法：分离 T1DM 未发病及发病 NOD小鼠的胰岛细胞，提取其总RNA后，与瑞士 Roche NimbleGen公司的12×135K基因表达谱芯片杂交。采用NimbleScan软件分析表达数据。结果：未发病NOD小鼠组和发病NOD小鼠组共有1007个差异表达基因。基因本体（gene ontology ，GO ）分析显示，在生物学过程方面，上调基因中87．7％与代谢相关，下调基因中18．97％与代谢相关；在细胞组分方面，29．20％的上调基因与细胞及细胞成分相关，78．08％的下调基因与细胞骨架、微管细胞骨架相关；在分子功能方面，84．07％的上调基因与结合有关，30．77％下调基因与水解酶活性相关。Pathw ay分析显示，上调的信号通路主要为黏蛋白型O聚糖合成信号通路，下调的信号通路主要为血管加压素信号通路。结论：T1DM 发病NOD小鼠和未发病NOD小鼠的胰岛细胞的基因表达水平有明显差异。%Objective:To explore the genetic changes in non‐obese diabetic (NOD ) mice during the development of Type 1 diabetes mellitus (T1DM ) with gene expression microarrays .Methods :The pancreatic islet cells of NOD mice without or with T1DM were isolated .Total RNA was extracted separately ,and hybridized with 12 × 135K gene expression microarrays (Roche NimbleGen Inc .) .NimbleScan software was used for data analysis of gene expression .Results:A total of 1007 differentially expressed genes were obtained from non‐diabetic and diabetic NOD mice .The gene ontology(GO) analysis showed that ,on aspect of biological processes ,87 .7% of the up‐regulated genes were associated with metabolism ,while 18 .97% of the down‐regulated genes were associated with metabolism .On aspect of cellular components ,29 .20% of the up‐regulated genes were associated with cells and cell components ,while 78 .08% of the down‐regulated genes were associated with cytoskeleton and microtubule cytoskeleton .On aspect of molecular function ,84 .07% of the up‐regulated genes were associated with binding , while 30 .77% of the down‐regulated genes were hydrolase activity related genes .The pathway analysis showed that the main signaling pathway for up‐regulating was mucin type O‐Glycan biosynthesis pathway ,and the main signaling pathway for down‐regulating was vasopressin pathway .Conclusions :There are significant differences in gene expression profile of pancreatic islet cells between NOD mice with T1DM and NOD mice without T1MD .