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

Ann Neurol. 1993 Jul;34(1):48-56. doi: 10.1002/ana.410340110.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Animals
  • Disease Models, Animal*
  • Female
  • Humans
  • Immunoglobulins / biosynthesis
  • In Situ Hybridization, Fluorescence
  • Lymphocyte Transfusion
  • Male
  • Mice
  • Mice, SCID / immunology*
  • Motor Endplate / immunology
  • Myasthenia Gravis / immunology*
  • Receptors, Cholinergic / immunology

Substances

  • Immunoglobulins
  • Receptors, Cholinergic