自发性狼疮小鼠高IgG血症遗传易感基因定位及多态性分析

Susceptibility Allele Mapping of IgG Hypergammaglobulinemia and Analysis of Polymorphism in Spontaneous Lupus Mice

目的 :定位自发性狼疮小鼠高 Ig G血症遗传易感基因 ,并比较自身与非自身免疫病小鼠间该易感基因是否存在多态性。方法 :建立 (NZB× NZW) F1 × NZW回交小鼠模型 ,采用覆盖小鼠 19条染色体的微卫星多态标记及数量性状位点 (QTL)分析进行基因定位 ,并应用扩增片段长度多态性分析 (Am p FL P)比较该易感基因的多态性。结果 :高 Ig G血症易感基因与小鼠 1号染色体末端微卫星多态标记 Dl Mit36肯定连锁 (L ods值 >3) ,该位点附近存在Fcgr2 b基因 ,且回交小鼠 Fcgr2 b基因 B/ W型组血清总 Ig G水平明显高于 W/ W型组 (P <0 .0 0 0 1) ;自身免疫病NZB小鼠 Fcgr2 b基因启动子区核酸片段长度短于非自身免疫病 NZW、C5 7BL/ 6及 BAL B/ C小鼠。结论 :(NZB×NZW) F1 小鼠高 Ig G血症易感基因为 NZB来源的 Fcgr2 b基因。

Objective:Our paper was to map the susceptibility allele of IgG hypergammaglobulinemia in systemic lupus erythematosus (SLE) model—(NZB×NZW)F 1 mice and compare the polymorphism of susceptibility allele between the autoimmune disease mice and non autoimmune disease mice. Methods:We set up the (NZB×NZW)F 1×NZW backcross mice model and used polymorphic microsatellite markers and quantitative trait locus (QTL)analysis as well as analysis of amplified fragment length polymorphism. Results:(1) Susceptibility allele of IgG hypergammaglobulinemia was localized the telomeric region on chromosome 1 which is linked to Fcgr2b gene according to the QTL analysis. The level of serum IgG in the group of Fcgr2b gene B/W type was higher than that of W/W type. (2) The length of Fcgr2b gene promotor nucleotide fragment in NZB mice was shorter than that in NZW、BALB/C、C57BL/6 mice. Conclusion: Susceptibility allele of IgG hypergammaglobulinemia in (NZB×NZW)F 1 mice was Fcgr2b gene derived NZB strain. NZB mice may have deletion in promotor region of Fcgr2b gene.