title: Delayed synapsing muscles are more severely affected in an experimental model of MuSK-induced myasthenia gravis.
abstract: Myasthenia gravis can be induced in mice by injecting the extracellular domain of rat muscle-specific kinase (MuSK), a transmembrane receptor tyrosine kinase involved in agrin signaling at the neuromuscular junction. About 5-10% of human myasthenia gravis patients have autoantibodies against MuSK. Here we have examined mouse neuromuscular junctions following MuSK immunization in two groups of muscles that can be distinguished on the basis of the timing of neuromuscular synaptogenesis and their response to perturbation of agrin signaling. We used confocal microscopy to characterize the distribution and expression of nicotinic acetylcoline receptors and of two presynaptic makers, neurofilament protein and synaptophysin. We observed disruption of neuromuscular junctions in all muscles examined in this model of myasthenia gravis. However delayed-synapsing muscles, including the diaphragm, sternomastoid and tibialis posterior, were significantly more severely affected than fast-synapsing muscles, including the intercostal, adductor longus and tibialis anterior. These results suggest a basis for the differential susceptibility of muscles in different classes of myasthenia gravis patients, including patients with autoantibodies against MuSK.
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5001, USA.
authors.forename: K
authors.initials: K
authors.lastname: Xu
authors.forename: S
authors.initials: S
authors.lastname: Jha
authors.forename: W
authors.initials: W
authors.lastname: Hoch
authors.forename: S E
authors.initials: SE
authors.lastname: Dryer
mesh_terms: D018171:Agrin / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal / Q000379:methods; D009132:Muscles / Q000378:metabolism / Q000473:pathology*; D009157:Myasthenia Gravis / Q000139:chemically induced / Q000473:pathology*; D016900:Neurofilament Proteins / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors
chemical_list: D018171:Agrin; D016900:Neurofilament Proteins; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D016708:Synaptophysin; C475048:MuSK protein, rat; D020794:Receptor Protein-Tyrosine Kinases