A polygene network in collagen disease

The pathological findings in collagen disease, which was originally proposed by Klemperer et al. in 1942, show complex lesions with glomerulonephritis, vasculitis, polyarthritis and/or sialoadenitis etc. It is still controversial whether such diversity and similarity of the lesions among collagen diseases depend on an ambiguity in diagnosis or an intrinsic quality of the diseases. In the study of susceptibility loci to collagen disease in MRL mouse models, we learned that several lesions such as glomerulonephritis, vasculitis, arthritis and sialoadenitis 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 each lesion in an additive manner with a hierarchical effect. Some of the susceptibility loci seemed to be common to those in other collagen diseases as well. Some of the positional candidate genes showed an allelic polymorphism in the coding region, possibly causing a qualitative difference in their 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 lesions, and also a regular variation of collagen disease. This is designated as the polygene network in collagen disease.