TY - JOUR
T1 - Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors - Recommendations for methods and experimental designs
AU - Losen, Mario
AU - Martinez-Martinez, Pilar
AU - Molenaar, Peter C.
AU - Lazaridis, Konstantinos
AU - Tzartos, Socrates
AU - Brenner, Talma
AU - Duan, Rui-Sheng
AU - Luo, Jie
AU - Lindstrom, Jon
AU - Kusner, Linda
PY - 2015/8
Y1 - 2015/8
N2 - Myasthenia gravis (MG) with antibodies against the acetylcholine receptor (AChR) is characterized by a chronic, fatigable weakness of voluntary muscles. The production of autoantibodies involves the dysregulation of T cells which provide the environment for the development of autoreactive B cells. The symptoms are caused by destruction of the postsynaptic membrane and degradation of the AChR by IgG autoantibodies, predominantly of the G1 and G3 subclasses. Active immunization of animals with AChR from mammalian muscles, AChR from Torpedo or Electrophorus electric organs, and recombinant or synthetic AChR fragments generates a chronic model of MG, termed experimental autoimmune myasthenia gravis (EAMG). This model covers cellular mechanisms involved in the immune response against the AChR, e.g. antigen presentation, T cell-help and regulation, B cell selection and differentiation into plasma cells. Our aim is to define standard operation procedures and recommendations for the rat EAMG model using purified AChR from the Torpedo californica electric organ, in order to facilitate more rapid translation of preclinical proof of concept or efficacy studies into clinical trials and, ultimately, clinical practice.
AB - Myasthenia gravis (MG) with antibodies against the acetylcholine receptor (AChR) is characterized by a chronic, fatigable weakness of voluntary muscles. The production of autoantibodies involves the dysregulation of T cells which provide the environment for the development of autoreactive B cells. The symptoms are caused by destruction of the postsynaptic membrane and degradation of the AChR by IgG autoantibodies, predominantly of the G1 and G3 subclasses. Active immunization of animals with AChR from mammalian muscles, AChR from Torpedo or Electrophorus electric organs, and recombinant or synthetic AChR fragments generates a chronic model of MG, termed experimental autoimmune myasthenia gravis (EAMG). This model covers cellular mechanisms involved in the immune response against the AChR, e.g. antigen presentation, T cell-help and regulation, B cell selection and differentiation into plasma cells. Our aim is to define standard operation procedures and recommendations for the rat EAMG model using purified AChR from the Torpedo californica electric organ, in order to facilitate more rapid translation of preclinical proof of concept or efficacy studies into clinical trials and, ultimately, clinical practice.
KW - Myasthenia gravis
KW - Experimental autoimmune myasthenia gravis
KW - Rat
KW - Torpedo californica
KW - Acetylcholine receptor
U2 - 10.1016/j.expneurol.2015.03.010
DO - 10.1016/j.expneurol.2015.03.010
M3 - Article
C2 - 25796590
SN - 0014-4886
VL - 270
SP - 18
EP - 28
JO - Experimental Neurology
JF - Experimental Neurology
ER -