Genetic control of autoimmune myocarditis mediated by myosin-specific antibodies

Autoimmune disease involves both the development of autoreactivity and the expression of organ damage, and susceptibility is genetically complex. We r ecently reported that in autoimmune myocarditis susceptibility to antibody- mediated cardiac injury is strain specific. DBA/2 mice develop myocarditis following administration of myosin-specific antibody, while BALB/c mice do not. This susceptibility appears to be controlled by expression of myosin i n the myocardial extracellular matrix. CByD2F1 mice are both resistant to i nduction of myocarditis and do not demonstrate extracellular myosin indicat ing a recessive genetic component to these traits. A backcross analysis of susceptibility using DBA/2 x CByD2F1 mice revealed a locus on chromosome 12 that is strongly linked with myocarditis, In male mice there was a second region on chromosome 1 that also contributes to disease susceptibility. How ever, genetic susceptibility in both female and male mice was genetically c omplex. This study demonstrates that the genetic basis of tissue injury can be analyzed separately from the genetic basis of autoreactivity, Future st udies will determine whether the genetic factors identified in this study a re also involved in susceptibility to rheumatic fever.