-ABSTRACT A new model of an autoimmune disease of the neuromuscular junction was obtained by injection of acetylcholine receptor purified from rat denervated muscles into Balb/c mice. Anti-rat, then anti-mouse acetylcholine receptor antibodies, appear in mouse serum during the immunization procedure. Electrophysiological investigations performed on immunized mice reveal a neuromuscular block similar to that found in myasthenia gravis. Not a single mouse with objective signs of muscular weakness was lacking anti-mouse acetylcholine receptor antibodies but no correlation was found between their level and the severity of the disease.Numerous animal models sharing many similarities with human myasthenia gravis have been reported. Rabbits (1-7), rats (5,8,9), guinea pigs (5, 9) monkeys (10), and goats (5) were immunized with acetylcholine receptor (AcChR) purified from the electric organ of Electrophorus electricus (1, 5-7, 9), Torpedo californica (9, 10), or Torpedo marmorata (2-4). These animals showed muscular weakness due to impaired neuromuscular transmission. Their sera contained high concentrations of antibodies directed against the antigen injected. The demonstration that sera from such immunized rabbits (7,11) or rats (8) either block the response of electroplax to carbamylcholine (7, 11) or decrease extrajunctional acetylcholine sensitivity of muscle fibers from denervated rat hemidiaphragm (8) suggests that anti-AcChR antibodies could act themselves as nicotinic blocking agents. Consequently, the paralysis observed in the experimental model could be due to an autoimmune response, the animal making antibodies against its own AcChR. If this were true, one should be able to detect in such experimental models autoantibodies as well as antibodies against the injected antigen. In fact, the presence of autoantibodies has been reported in the serum of rats with experimental autoimmune myasthenia gravis (9). However, compared to the level of antibodies directed against eel AcChR, the amount of anti-rat AcChR is much lower, and differs from the former by a factor greater than one thousand (9). This is probably due to the fact that antigen and host are phylogenetically distant. To Preparation of a-Bungarotoxin (a-Bgt). The crude venom of Bungarus multicinctus was obtained from Miami Serpentarium Laboratories (lot BM 31-1) and purified on carboxymethyl-Sephadex C-50 (Pharmacia) according to the procedure described by Lee et al. (12). Contaminants were removed by further chromatography, first on Sephadex G-50 M (Pharmacia), then on carboxymethylcellulose (CM-32, Whatman), with a shallow linear gradient (ammonium acetate 0.05 M at pH 5 to 0.5 M at pH 7). a-Bgt was iodinated to specific activities of Ci/mmol by a method using chloramine-T which gives 98% of the labeled product as monoiodinated derivaitive (13).Free iodine was removed by chromatography on Biogel P4 (Biorad).Preparation of AcChR. Rat AcChR was extracted from denervated muscle by the method of Almon et al. (14), and further purified by affinity chromatog...