SLE模型小鼠高IgG血症易感基因-Fcgr2b基因突变及对其表达的影响

目的:测定系统性红斑狼疮(SLE)小鼠模型 (NZB×NZW)F1双亲NZB ,NZW小鼠Fcgr2b基因启动子区核酸序列及其表达的改变,明确Fcgr2b基因的突变性质、对该基因表达的影响及与高IgG血症的关系。方法:采用核酸序列分析测定NZB ,NZW小鼠Fcgr2b基因启动子区突变性质;RT PCR检测Fcgr2b基因表达的改变;ELISA法测定比较(NZB×NZW)F1,NZB和NZW小鼠及(NZB×NZW)F1×NZW回交小鼠Fcgr2b基因B/W型与W /W型组间血清总IgG水平。结果:NZB小鼠Fcgr2b基因启动子区与正常鼠BALB/c相比存在2个部位碱基缺失,分别为13bp及3bp。NZW小鼠除有3个碱基置换外,与BALB/c鼠该基因启动子区序列相同;NZB小鼠Fcgr2b基因mRNA的表达较正常鼠BALB/c降低;NZB小鼠血清总IgG水平明显高于NZW小鼠(P <0 0 5 ) ,回交小鼠Fcgr2b基因B/W型组血清总IgG水平明显高于W/W型组(P <0 0 0 0 1)。结论:NZB小鼠Fcgr2b基因启动子区存在碱基缺失,且该缺失突变可引起其表达的降低而导致高IgG血症

Gene mutation and its effects of IgG hypergammaglobulinemia susceptibility gene-Fcgr2b gene in model of systemic lupus erythematosus

Objective:To determine nucleotide sequence of susceptibility allele of IgG hypergammaglobulinemia-Fcgr2b gene and the mRNA expression of Fcgr2b in SLE model. To understand the nature of Fcgr2b deletion and the relationship with the hyper-IgG.Methods:Nucleotide sequence analysis was used to locate mutation site of Fcgr2b gene, expression of Fcgr2b mRNA was analyzed by RT-PCR and the serum IgG of the group of Fcgr2b gene B/W type and W/W type were measured by ELISA.Results:Compared with BALB/c nucleotide sequence of normal mouse,2 deletion sites were found in Fcgr2b gene promoter region in NZB mice and changes of 3 base pairs were found in NZW mice. The expression of Fcgr2b mRNA in NZB was lower than in normal mice-BALB/c. Serum total IgG of the group of Fcgr2b gene B/W type was obviously higher than that of W/W type( P <0 000 1).Conclusion:There were two deletion sites in Fcgr2b gene promoter region in NZB mice and the deletions could induce decreasing of the expression of Fcgr2b mRNA that lead to hyper-IgG.