Pax-8基因敲除小鼠心脏中NR4A1基因表达上调  

Up-regulation of NR4A1 gene expression in Pax-8 gene knockout mice myocardium

作　　者：黄晓燕[1] 高瞻[1] 周希[1] 梁万前 陈锡文[2] 陈通克[2] 杨德业[1] 

机构地区：[1]温州医学院附属第一医院心内科温州医学院心血管生物和基因研究所,浙江温州325000 [2]温州医学院实验动物中心,浙江温州325035

出　　处：《温州医学院学报》2011年第3期205-208,共4页Journal of Wenzhou Medical College

基　　金：国家自然科学基金资助项目(30571050)

摘　　要：目的:寻找先天性心脏病室间隔缺损相关基因——转录因子Pax-8保护细胞凋亡的途径。方法:提取Pax-8基因敲除小鼠纯合子(Pax-8 KO-/-)和杂合子(Pax-8 KO+/-)的心脏总RNA,利用小鼠基因的基因芯片检测两组小鼠基因表达水平,找出差异表达的基因,并经半定量RT-PCR和荧光实时定量PCR技术初步筛选出转录因子Pax-8的下游基因。结果:基因芯片检测发现,与Pax-8 KO+/-组相比,在Pax-8 KO-/-小鼠中有25个基因表达下调,17个基因表达上调。用半定量RT-PCR验证发现,nuclear receptor sub-family4,group A,member 1(NR4A1)基因在Pax-8 KO-/-组上调。定量RT-PCR亦证实在Pax-8 KO-/-组NR4A1基因的表达水平较Pax-8 KO+/-组及Pax-8+/+(野生型)组分别上调1.53倍和4.79倍(P<0.01)。结论:NR4A1基因受Pax-8基因调控,在Pax-8保护细胞凋亡途径中发挥作用。Objective： To find the possible genic pathway for the anti-apoptosis function of the ventricular septal defeet related to Pax-8.Method： The total RNA derived from the heart of Pax-8 KO-/-and Pax-8 KO＋/-mice was extracted.Mouse genome DNA microarray was used to detect the differential expression level between the Pax-8 KO-/-and the Pax-8 KO＋/-mice heart.The candidate genes were confirmed by RT-PCR and real time RT-PCR assay.Results： Microarray results showed that 25 genes were down-regulated and 17 were up-regulated in the Pax-8 KO-/-mice compared to the Pax-8 KO＋/-mice.Nuclear receptor subfamily 4,group A,member 1（NR4A1）was proved to be up-regulated by RT-PCR in the Pax-8 KO-/-mice heart.Real time RT-PCR results revealed that NR4A1 in the Pax-8 KO-/-mice was 1.53 and 4.79 fold as much as in the Pax-8 KO＋/-and the Pax-8＋/＋ mice（P 0.01）.Conclusion： The NR4A1 gene is one of the downstream genes of the Pax-8 and probably evolved and played an important role in the mechanism of ventricular septum defect.

关 键 词：NR4A1 室间隔缺损 细胞凋亡 pairedboxgene8 小鼠 

分 类 号：R363.1[医药卫生—病理学]