COISOGENIC ALL-PLUS-ONE IMMUNIZATION - A MODEL FOR IDENTIFYING MISSING PROTEINS IN NULL-MUTANT CONDITIONS - ANTIBODIES TO DYSTROPHIN IN MDXMOUSE AFTER TRANSPLANTATION OF MUSCLE FROM NORMAL COISOGENIC DONOR

Specific antibody response against an alien protein is one of the basi c immunologic mechanisms in immunecompetent organisms. They can be use d as a first step in various approaches leading to the identification of proteins or even an antigen-encoding gene. Accordingly: we wanted t o find out whether a null-mutant immunecompetent organism would produc e specific antibodies against the missing gene product. We chose the m ouse mutant mdx (X-linked muscular dystrophy) which represents a null mutant condition for the gene product of the Duchenne muscular dystrop hy (DMD) gene, dystrophin. When dystrophin-deficient mdx mice received dystrophin-containing muscle grafts from coisogenic normal mice, high titres of antibodies specific for dystrophin were detected in the tra nsplanted animals' sera. Because dystrophin-containing muscle grafts w ere not rejected but have properly regenerated even in the presence of high titre antibodies against dystrophin, these findings have importa nt bearings on all therapeutical strategies based on dystrophin supple mentation. Using the mdx mouse as a null-mutant model we showed that t here was no immune tolerance for the missing protein but specific anti bodies were produced when the organism came in contact with this prote in. This simple approach may serve as a shortcut for identifying missi ng proteins presumably not only in neuromuscular disorders but in a wi de range of diseases where null-mutant animal models and corresponding coisogenic inbred strains exist.