Fig. 10

Model for NMJ and muscle pathology in SBMA mouse models. NMJ pathology reflects the contractile properties of the motor unit and metabolic machinery of the muscle fiber. We hypothesize that differences in the developmental subtype of the muscle also contributes to the response to disease. Slow-twitch soleus NMJs showed significant pre- and post-synaptic changes, with modest muscular pathology. Fast-twitch TA and gastrocnemius showed differing levels of NMJ pathology despite severe muscle atrophy and metabolic changes in both muscles. TA NMJs showed primarily post-synaptic pathology, while gastrocnemius showed significant pre- and post-synaptic NMJ pathology. We hypothesize the lower level of NMJ pathology in TA is due to the fast-synapsing (FaSyn) properties of TA during development, compared to the delayed-synapsing (DeSyn) properties of gastrocnemius. Together, the contractile properties of the motor unit and the developmental properties of the muscle fiber contribute to NMJ pathology in SBMA mouse models