Muscle-specific kinase (MuSK) autoantibodies suppress the MuSK pathway and ACh receptor retention at the mouse neuromuscular junction
Nazanin Ghazanfari, Marco Morsch, Stephen W Reddel, Simon X Liang, William D Phillips
JOURNAL OF PHYSIOLOGY-LONDON | WILEY | Published : 2014
Muscle-specific kinase (MuSK) autoantibodies from myasthenia gravis patients can block the activation of MuSK in vitro and/or reduce the postsynaptic localization of MuSK. Here we use a mouse model to examine the effects of MuSK autoantibodies upon some key components of the postsynaptic MuSK pathway and upon the regulation of junctional ACh receptor (AChR) numbers. Mice became weak after 14 daily injections of anti-MuSK-positive patient IgG. The intensity and area of AChR staining at the motor endplate was markedly reduced. Pulse-labelling of AChRs revealed an accelerated loss of pre-existing AChRs from postsynaptic AChR clusters without a compensatory increase in incorporation of (newly sy..View full abstract
Awarded by National Health and Medical Research Council
This work was supported by the National Health and Medical Research Council (570930 to W.D.P and S.W.R.), the Brain Foundation, The Beeren Foundation, and the Australian Myasthenic Association in New South Wales.