Title:Mouse Models of Myasthenia Gravis
Volume: 21
Issue: 18
Author(s): Joanne Ban and William D. Phillips
Affiliation:
Keywords:
Autoantibodies, nicotinic receptors, antigenic modulation, membrane attack complex, muscle specific kinase, myasthenia gravis,
fatigue.
Abstract: Myasthenia gravis is a muscle weakness disease characterized by autoantibodies that target components
of the neuromuscular junction, impairing synaptic transmission. The most common form of myasthenia gravis involves
antibodies that bind the nicotinic acetylcholine receptors in the postsynaptic membrane. Many of the remaining
cases are due to antibodies against muscle specific tyrosine kinase (MuSK). Recently, autoantibodies against
LRP4 (another component of the MuSK signaling complex in the postsynaptic membrane) were identified as the
likely cause of myasthenia gravis in some patients. Fatiguing weakness is the common symptom in all forms of
myasthenia gravis, but muscles of the body are differentially affected, for reasons that are not fully understood.
Much of what we have learnt about the immunological and neurobiological aspects of the pathogenesis derives
from mouse models. The most widely used mouse models involve either passive transfer of autoantibodies, or active
immunization of the mouse with acetylcholine receptors or MuSK protein. These models can provide a robust
replication of many of the features of the human disease. Depending upon the protocol, acute fatiguing weakness develops 2 - 14 days after
the start of autoantibody injections (passive transfer) or might require repeated immunizations over several weeks (active models).
Here we review mouse models of myasthenia gravis, including what they have contributed to current understanding of the pathogenic
mechanisms and their current application to the testing of therapeutics.
