Identification of quantitative trait loci governing arthritis severity andhumoral responses in the murine model of Lyme disease

A spectrum of disease severity has been observed in patients with Lyme dise ase, with similar to 60% of untreated individuals developing arthritis. The murine model of Lyme disease has provided strong evidence that the genetic composition of the host influences the severity of arthritis following inf ection with Borrelia burgdorferi: infected C3H mice develop severe arthriti s while infected C57BL/6N mice develop mild arthritis. Regions of the mouse genome controlling arthritis severity and humoral responses during B, burg dorferi infection were identified in the F-2 intercross generation of C3H/H eNCr and C57BL/6NCr mice. Rear ankle swelling measurements identified quant itative trait loci (QTL) on chromosomes 4 and 5, while histopathological sc oring identified QTL on a unique region of chromosome 5 and on chromosome 1 1, The identification of QTL unique for ankle swelling or histopathological severity suggests that processes under distinct genetic control are respon sible for these two manifestations of Lyme arthritis. Additional QTL that c ontrol the levels of circulating Igs induced by B. burgdorferi infection we re identified on chromosomes 6, 9, 11, 12, and 17, Interestingly, the magni tude of the humoral response was not correlated with the severity of arthri tis in infected F, mice. This work defines several genetic loci that regula te either the severity of arthritis or the magnitude of humoral responses t o B, burgdorferi infection in mice, with implications toward understanding the host-pathogen interactions involved in disease development.