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. 2021 Mar 22;118(13):e2020635118. doi: 10.1073/pnas.2020635118

Fig. 2.

Fig. 2.

Monovalent MuSK antibodies induce rapid onset, progressive myasthenic symptoms in mice, whereas bivalent MuSK antibodies do not. (A) Experimental design of passive transfer with 2.5 mg/kg recombinant antibody. (B) Serum antibody titers confirmed exposure. (C–E) Monovalent, but not bivalent, MuSK antibodies induced progressive weight loss and muscle weakness. Bivalent 13–3B5 induced a delayed, mild loss of grip strength. (F and G) Monovalent, but not bivalent, MuSK antibodies induced a significantly larger CMAP decrement upon repetitive stimulation at 40 Hz compared with the b12 control. (H) Ex vivo tetanic contraction force of the diaphragm was reduced by 13–3B5, 13–3B5xb12, and 11–3F6xb12 compared with b12. (I) The safety factor of neuromuscular transmission was assessed in the presence of 125 nM dTC. Exposure to all MuSK antibodies reduced the safety factor compared with the b12 control, although for 11–3F6 this was only a trend (P = 0.079). 11–3F6 and 11–3F6xb12: n = 6; 13–3B5: n = 5; 13–3B5xb12 and b12: n = 6 (hanging time n = 5). Data represent mean ± SEM. One-way ANOVA with Šidák-corrected comparisons for all parameters (C, D, G, H, and I) except hanging time, for which Kruskal–Wallis test was used (C). *P < 0.05, **P < 0.01, *** <0.001, ****P < 0.0001 compared with b12 group, unless otherwise specified.