PMID- 29125188
OWN - NLM
STAT- MEDLINE
DCOM- 20190729
LR  - 20190729
IS  - 1749-6632 (Electronic)
IS  - 0077-8923 (Linking)
VI  - 1412
IP  - 1
DP  - 2018 Jan
TI  - The mouse passive-transfer model of MuSK myasthenia gravis: disrupted MuSK 
      signaling causes synapse failure.
PG  - 54-61
LID - 10.1111/nyas.13513 [doi]
AB  - While the majority of myasthenia gravis patients express antibodies targeting the 
      acetylcholine receptor, the second most common cohort instead displays 
      autoantibodies against muscle-specific kinase (MuSK). MuSK is a transmembrane 
      tyrosine kinase found in the postsynaptic membrane of the neuromuscular junction. 
      During development, MuSK serves as a signaling hub, coordinating the alignment of 
      the pre- and postsynaptic components of the synapse. Adult mice that received 
      repeated daily injections of IgG from anti-MuSK(+) myasthenia gravis patients 
      developed muscle weakness, associated with neuromuscular transmission failure. 
      MuSK autoantibodies are predominantly of the IgG4 type. They suppress the kinase 
      activity of MuSK and the phosphorylation of target proteins in the postsynaptic 
      membrane. Loss of postsynaptic acetylcholine receptors is the primary cause of 
      neuromuscular transmission failure. MuSK autoantibodies also disrupt the capacity 
      of the motor nerve terminal to adaptively increase acetylcholine release in 
      response to the reduced postsynaptic responsiveness to acetylcholine. The passive 
      IgG transfer model of MuSK myasthenia gravis has been used to test candidate 
      treatments. Pyridostigmine, a first-line cholinesterase inhibitor drug, 
      exacerbated the disease process, while 3,4-diaminopyridine and albuterol were 
      found to be beneficial in this mouse model.
CI  - (c) 2017 New York Academy of Sciences.
FAU - Ghazanfari, Nazanin
AU  - Ghazanfari N
AD  - Physiology and Bosch Institute, University of Sydney, Sydney, New South Wales, 
      Australia.
FAU - Trajanovska, Sofie
AU  - Trajanovska S
AD  - Physiology and Bosch Institute, University of Sydney, Sydney, New South Wales, 
      Australia.
FAU - Morsch, Marco
AU  - Morsch M
AD  - Physiology and Bosch Institute, University of Sydney, Sydney, New South Wales, 
      Australia.
AD  - Department of Biomedical Sciences, Macquarie University, Sydney, New South Wales, 
      Australia.
FAU - Liang, Simon X
AU  - Liang SX
AD  - Department of Biochemistry and Molecular Biology, College of Basic Medical 
      Sciences, Liaoning Medical University, Jinzhou, China.
FAU - Reddel, Stephen W
AU  - Reddel SW
AD  - Department of Molecular Medicine, Concord Hospital, Sydney, New South Wales, 
      Australia.
FAU - Phillips, William D
AU  - Phillips WD
AD  - Physiology and Bosch Institute, University of Sydney, Sydney, New South Wales, 
      Australia.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20171110
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Muscle Proteins)
RN  - 0 (Receptors, Cholinergic)
RN  - 0 (peripheral membrane protein 43K)
RN  - EC 2.7.10.1 (MuSK protein, mouse)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
MH  - Animals
MH  - Cholinesterase Inhibitors/pharmacology
MH  - Female
MH  - Humans
MH  - Immunization, Passive
MH  - Mice
MH  - Muscle Proteins/metabolism
MH  - Myasthenia Gravis, Autoimmune, Experimental/*etiology/immunology/physiopathology
MH  - Receptor Protein-Tyrosine Kinases/*antagonists & 
      inhibitors/*immunology/physiology
MH  - Receptors, Cholinergic/immunology/metabolism
MH  - Synapses/immunology/physiology
OTO - NOTNLM
OT  - mouse models
OT  - muscle-specific kinase
OT  - myasthenia gravis
OT  - neuromuscular disease
OT  - neuromuscular junction
EDAT- 2017/11/11 06:00
MHDA- 2019/07/30 06:00
CRDT- 2017/11/11 06:00
PHST- 2017/07/25 00:00 [received]
PHST- 2017/09/05 00:00 [revised]
PHST- 2017/09/09 00:00 [accepted]
PHST- 2017/11/11 06:00 [pubmed]
PHST- 2019/07/30 06:00 [medline]
PHST- 2017/11/11 06:00 [entrez]
AID - 10.1111/nyas.13513 [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2018 Jan;1412(1):54-61. doi: 10.1111/nyas.13513. Epub 2017 Nov 
      10.