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Salk Institute for Biological Studies (Drs. Shelton and Lindstrom), San Diego, CA; and the Department of Anatomy, School of Veterinary Medicine, University of California (Dr. Cardinet), Davis, CA.
Serum from 35 cases of naturally occurring acquired canine myasthenia gravis (MG) were assayed for patterns of autoantibody specificities against canine acetylcholine receptor (AChR) using monoclonal antibodies (mAbs) and antiserum against defined regions of the AChR as competitive inhibitors of autoantibody binding. In human MG patients and in animals immunized with AChR purified from fish electric organs or mammalian muscle, most of the antibodies are directed against the main immunogenic region (MIR), a conformationally dependent region located on the extracellular surface of the a subunit away from the ACh binding site. In our studies using canine MG serum, we found that, as in human MG and in animals immunized with AChR, the antibody response is heterogeneous and predominantly IgG, with a large proportion of the autoantibodies directed against the MIR. The mAbs to the MIR blocked an average of 68% of serum antibody binding. A mAb to the 
subunit and polyclonal antiserum to the subunit blocked an average of 34% and 39% of serum antibody binding, respectively, indicating that these subunits also contain relevant antigenic determinants, a pattern that has also been observed in human MG serum. Anti-
bungarotoxin binding site antibodies made up only a small fraction of the autoantibody population in canine MG as in human MG. These and other features described here suggest that canine MG is a useful model of human MG.
Address correspondence and reprint requests to Dr. Lindstrom, The Salk Institute, PO Box 85800, San Diego, CA 92138.
G.D.S. is supported by a fellowship from the California Chapter of the Myasthenia Gravis (MG) Foundation. Research on MG in J.L.'s laboratory is supported by grants from the NIH (NS11323), the Muscular Dystrophy Association, the Alexander Onassis Public Benefit Foundation, the Los Angeles and California Chapters of the MG Foundation, and the Companion Animal Laboratory, School of Veterinary Medicine, University of California-Davis.
Received November 5, 1987. Accepted for publication in final form January 29, 1988.
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