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目的:探讨与狼疮性肾炎相关的新西兰黑鼠(NZB)易感基因染色体位点。方法:通过建立(NZB×NZW)F1×NZW回交小鼠模型,以尿蛋白为狼疮性肾炎表现型,利用微卫星遗传标记进行基于数量性状位点(QTL)分析的全基因组扫描方法,寻找源于NZB的遗传易感基因位点并确定染色体位置。结果:根据QTL分析发现两个与狼疮鼠蛋白尿发生有关的易感基因位点,分别位于NZB小鼠第4号染色体的D4Mit71区域及第17号染色体D17Mit22区域(LOD>3.3)。同时携有两个NZB位点的小鼠尿蛋白阳性率最高,而只有一个位点的小鼠其尿蛋白阳性率较NZW纯合鼠也明显增高(P<0.005)。结论:NZB第4号染色体的D4Mit71区域及第17号染色体的D17Mit22区域可能为(NZB×NZW)F1×NZW回交鼠狼疮性肾炎蛋白尿易感位点。两个位点之间具有协同增效作用。
Objective: To investigate the chromosomal location of New Zealand black rat (NZB) susceptibility gene associated with lupus nephritis. Methods: The urinary protein was used as the phenotype of lupus nephritis by establishing the (NZB × NZW) F1 × NZW backcross mouse model and the whole genome scanning method based on quantitative trait locus (QTL) analysis was used to find the From the genetically susceptible loci of NZB and to determine the chromosomal location. RESULTS: Two QTLs for susceptibility to proteinuria in lupus mice were found in the D4Mit71 region on chromosome 4 and the D17Mit22 region on chromosome 17 (LOD> 3.3). The positive rate of urinary protein in the two NZB loci was the highest at the same time, but the positive rate of urinary protein in the one locus was significantly higher than that of NZW homozygous (P <0.005). CONCLUSION: The D4Mit71 region of chromosome 4 on chromosome 4 and the region of D17Mit22 on chromosome 17 may be (NZB × NZW) F1 × NZW proteinuria susceptibility loci in lupus nephritis. There is synergy between the two loci.