Genomics of Vasculitis: Lessons from Mouse Models

摘要

>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 found that systemic vasculitis developed through the cumulative effect of multiple gene loci, each of which by itself did not have a significant effect in inducing the related phenotype, thus indicating a polygenic system. The mice developed vasculitis in an additive manner with a hierarchical effect. Some of the susceptibility loci seemed to be common to those in other collagen diseases. 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. (J Jpn Coll Angiol, 2009, 49: 11-16)