Nose Masato
Department of Pathogenomics, Ehime University Graduate School of Medicine, Ehime, Japan.
Allergol Int. 2007 Jun;56(2):79-86. doi: 10.2332/allergolint.r-04-140. Epub 2007 May 1.
In addition to the studies of cellular and molecular events in the pathogenesis of systemic vasculitis, a genome analysis of mouse models may shed some light on the complex clinicopathological manifestations of systemic vasculitis. In the study of susceptibility loci to vasculitis in MRL mouse models, we learned that systemic vasculitis developed in a cumulative effect of multiple gene loci, each of which by itself did not have a significant effect to induce the related phenotype, thus indicating a polygenic system. The mice developed vasculitis in an additive manner of multiple genes with a hierarchical effect. Some of the susceptibility loci seemed to be common to those in other collagen diseases as well. Moreover, the loci controlling tissue specificity of vasculitis were present. One of the positional candidate genes for vasculitis showed an allelic polymorphism in the coding region, thus possibly causing a qualitative difference in its function. As a result, a particular combination of polygenes with such an allelic polymorphism may thus play a critical role in leading the cascade reaction to develop vasculitis, and also a regular variation of systemic vasculitis. This is designated as the polygene network in systemic vasculitis.
除了对系统性血管炎发病机制中的细胞和分子事件进行研究外，对小鼠模型的基因组分析可能会为系统性血管炎复杂的临床病理表现提供一些线索。在MRL小鼠模型中对血管炎易感基因座的研究中，我们了解到系统性血管炎是由多个基因座的累积效应发展而来的，其中每个基因座本身对诱导相关表型并没有显著影响，因此表明这是一个多基因系统。小鼠以多个基因的累加方式并具有层级效应发展出血管炎。一些易感基因座似乎在其他胶原病中也很常见。此外，还存在控制血管炎组织特异性的基因座。血管炎的一个定位候选基因在编码区显示出等位基因多态性，因此可能导致其功能上的质的差异。结果，具有这种等位基因多态性的多基因的特定组合可能在引发级联反应以发展血管炎以及系统性血管炎的规律性变化中起关键作用。这被称为系统性血管炎中的多基因网络。
