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目的 :探讨新西兰白鼠 (NZW)狼疮性肾炎 (LN)的遗传易感基因。 方法 :建立 (NZBxNZW )F1xNZB回交小鼠模型 ,采用覆盖小鼠除性染色体以外全部 19条染色体的多态性微卫星遗传标记及数量性状位点 (QTL)分析进行基因定位 ,并应用限制性长度多态方法比较LN易感基因的多态性 ,将小鼠的累积蛋白尿定性作为LN的表现型。 结果 :QTL分析结果显示 ,(NZBxNZW)F1xNZB回交小鼠LN易感基因位点分别与NZW小鼠第 11染色体微卫星遗传标记D11Mit2 6 3及 17染色体微卫星遗传标记D17Mit6 1肯定连锁 (Lod值 >3)。D11Mit2 6 3位点附近存在粒细胞集落刺激因子 3基因 ,D17Mit6 1位点附近存在 (TNF)α和H 2基因。同时携有D17Mit6 1基因B/W型和D11Mit2 6 3基因B/W型两个易感基因位点组的蛋白尿的阳性率比单基因组增高。 结论 :NZW来源的Csf3基因及TNFα(或H 2 )基因是新西兰小鼠LN重要的易感基因。易感基因之间有相互促进作用
Objective: To investigate the genetic susceptibility genes of New Zealand white rat (NZW) lupus nephritis (LN). Methods: The (NZBxNZW) F1xNZB backcross mice model was established. All the 19 microsatellite loci (QTLs) except for the sex chromosomes in mice were used for gene localization and restriction Polymorphism of LN was used to compare the polymorphism of LN susceptibility genes. The cumulative proteinuria of mice was used as the phenotype of LN. Results: The results of QTL analysis showed that the LN susceptibility loci in (NZBxNZW) F1xNZB backcross mice were positively linked with NZD mice chromosome 11 D11Mit2 6 3 and chromosome 17 microsatellite markers D17Mit6 1 (Lod value > 3). The presence of granulocyte colony stimulating factor 3 gene near the D11Mit2 6 3 locus and the presence of (TNF) α and H2 genes near the D17Mit6 locus 1. The positive rates of proteinuria in two susceptibility loci groups carrying both D17Mit6 1 gene B / W type and D11Mit2 6 3 gene type B / W gene were higher than that of the single genomic group. CONCLUSIONS: The NZW-derived Csf3 and TNFα (or H 2) genes are important predisposing genes for LN in mouse New Zealand. There is mutual promotion between susceptible genes