The human–severe combined immunodeficiency myasthenic mouse model: A new approach for the study of myasthenia gravis

G Martino, BL DuPont, RL Wollmann… - Annals of Neurology …, 1993 - Wiley Online Library
G Martino, BL DuPont, RL Wollmann, P Bongioanni, J Anastasi, J Quintans, BGW Arnason…
Annals of Neurology: Official Journal of the American Neurological …, 1993Wiley Online Library
We have established a new chimeric human‐mouse model of myasthenia gravis in severe
combined immunodeficiency mice, using human peripheral blood lymphocytes that survive
in the mouse and produce specific antibodies that mediate pathological changes typical of
human myasthenia gravis. Mice given peripheral blood lymphocytes from both anti–
acetylcholine receptor (AChR) antibody–positive and–negative patients with myasthenia
gravis showed circulating anti–acetylcholine receptor antibodies, deposition of human IgG at …
Abstract
We have established a new chimeric human‐mouse model of myasthenia gravis in severe combined immunodeficiency mice, using human peripheral blood lymphocytes that survive in the mouse and produce specific antibodies that mediate pathological changes typical of human myasthenia gravis. Mice given peripheral blood lymphocytes from both anti–acetylcholine receptor (AChR) antibody–positive and –negative patients with myasthenia gravis showed circulating anti–acetylcholine receptor antibodies, deposition of human IgG at muscle end‐plates, and simplification of the postsynaptic membrane, findings characteristic of human myasthenia gravis. Mice given human peripheral blood lymphocytes from healthy donors and simultaneously immunized with Torpedo acetylcholine receptor showed the same changes. This chimeric model, utilizing human cells to reproduce the immunopathological findings of human myasthenia gravis in a nonhuman environment, offers new opportunities to study immune regulation in autoimmunity.
Wiley Online Library