Genetic linkage of IgG autoantibody production in relation to lupus nephritis in New Zealand hybrid mice.
Genetic linkage of IgG autoantibody production in relation to lupus nephritis in New Zealand hybrid mice.
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DOI：
10.1172/jci118975
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发表时间：
1996-10
期刊：
影响因子：
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通讯作者：
T. Vyse;C. G. Drake;S. Rozzo;E. Roper;S. Izui;B. Kotzin
中科院分区：
文献类型：
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作者：
T. Vyse;C. G. Drake;S. Rozzo;E. Roper;S. Izui;B. Kotzin
新西兰黑（NZB）和新西兰白（NZW） F1杂交小鼠是人类系统性红斑狼疮的模型。这些小鼠发展为严重的免疫复合物介导的肾炎，其中抗核自身抗体被认为起主要作用。我们对（NZB x NZW）F1 x NZW回交小鼠进行遗传分析，以深入了解不同的自身抗体是否受到单独的遗传影响，并确定哪种自身抗体在狼疮样肾炎的发展中最重要。结果显示，一组基因座协调调节血清中针对双链DNA、单链DNA、总组蛋白和染色质的IgG抗体水平，与产生针对病毒糖蛋白gp70的自身抗体的基因座重叠。与抗核抗体相比，与抗gp70相关的位点与肾脏疾病的关联最强，提示gp70自身抗体是狼疮性肾炎模型的主要致病抗体。有趣的是，4号染色体远端位点Nba1与肾炎有关，但与测量的任何自身抗体无关，这表明它在自身抗体产生的远端检查点导致肾脏疾病。
F1 hybrids of New Zealand black (NZB) and New Zealand white (NZW) mice are a model of human systemic lupus erythematosus. These mice develop a severe immune com-plex-mediated nephritis, in which antinuclear autoantibodies are believed to play the major role. We used a genetic analysis of (NZB x NZW)F1 x NZW backcross mice to provide insight into whether different autoantibodies are subject to separate genetic influences and to determine which autoantibodies are most important in the development of lupus-like nephritis. The results showed one set of loci that coordinately regulated serum levels of IgG antibodies to double-stranded DNA, single-stranded DNA, total histones, and chromatin, which overlapped with loci that were linked to the production of autoantibodies to the viral glycoprotein, gp70. Loci linked with anti-gp70 compared with antinuclear antibodies demonstrated the strongest linkage with renal disease, suggesting that autoantibodies to gp70 are the major pathogenic antibodies in this model of lupus nephritis. Interestingly, a distal chromosome 4 locus, Nba1, was linked with nephritis but not with any of the autoantibodies measured, suggesting that it contributes to renal disease at a checkpoint distal to autoantibody production.