Myasthenia gravis induced in mice by immunization with the recombinant extracellular domain of rat muscle-specific kinase (MuSK).
Myasthenia gravis (MG) is mostly caused by anti-acetylcholine receptor (AChR) auto-antibodies (Abs). Such Abs are undetectable in 10-15% of MG patients, but many have anti-muscle-specific kinase (MuSK) Abs. We injected recombinant rat-MuSK extracellular domain in H-2(a), H-2(b), H-2(bm12) and H-2(d) mice. Certain strains exhibited exercise-induced fatigue, tremors, weight loss, and some died after 2-3 injections. Compound muscle action potentials showed decrement with low-frequency repetitive nerve stimulation. Miniature endplate potentials decreased, suggesting lower numbers of endplates functional AChRs. Myasthenic sera inhibited agrin-induced AChR aggregation in C2C12 myotubes.


CONCLUSIONS
Anti-MuSK Abs induce MG, which might also result from blocking the agrin-signaling pathway.
Jha
Smita
S
Department of Biology and Biochemistry, University of Houston, TX 77204, USA.
Xu
Kaiping
K
Maruta
Takahiro
T
Oshima
Minako
M
Mosier
Dennis R
DR
Atassi
M Zouhair
MZ
Hoch
Werner
W
D000200:Action Potentials / Q000276:immunology; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood; D002478:Cells, Cultured; D006224:Cricetinae; D045604:Extracellular Fluid / Q000201:enzymology* / Q000276:immunology; D005260:Female; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism; D009157:Myasthenia Gravis / Q000201:enzymology* / Q000276:immunology*; D017434:Protein Structure, Tertiary; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000008:administration & dosage* / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000008:administration & dosage* / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology
D001323:Autoantibodies; D011950:Receptors, Cholinergic; D011994:Recombinant Proteins; C475048:MuSK protein, rat; D020794:Receptor Protein-Tyrosine Kinases