A locus on chromosome 1 promotes susceptibility of experimental autoimmune myocarditis and lymphocyte cell death.

We previously identified by linkage analysis a region on chromosome 1 (Eam1) that confers susceptibility to experimental autoimmune myocarditis (EAM). To evaluate the role of Eam1, we created a congenic mouse strain, carrying the susceptible Eam1 locus of A.SW on the resistant B10.S background (B10.A-Eam1 congenic) and analyzed three outcomes: 1) the incidence and severity of EAM, 2) the susceptibility of lymph node cells (LNCs) to Cy-enhanced cell death, and 3) susceptibility of lymphocytes to antigen-induced cell death. Incidence of myocarditis in B10.A-Eam1 congenic mice was comparable to A.SW mice, confirming that Eam1 plays an important role in disease development. Caspase 3, 8 and 9 activation in LNCs following Cy treatment and in CD4(+) T cells after immunization with myosin/CFA was significantly lower in A.SW than B10.S mice whereas B10.A-Eam1 congenic mice exhibited an intermediate phenotype. Our results show that Eam1 reduces lymphocyte apoptosis and increases susceptibility to EAM.