Exclusion of Sorbs1 exon 25 in mice skeletal muscle disorganizes NMJ ultrastructural organization. Panels a and b are PBS‐treated tibialis anterior; panels c and d are U7‐ESE25–treated tibialis anterior. (a) Upper image is a NMJ from PBS‐treated tibialis at 2 months post injection. The upper part of the neuronal presynaptic bouton is recovered by a terminal Schwann cell process and faces numerous well‐ordered parallel post‐synaptic junctional folds. (c) NMJs from U7‐ESE25–treated tibialis at 2 months post injection. Presynaptic boutons appear normal with numerous synaptic vesicles and mitochondria, while there is a reduction of post‐junctional fold density with rare and short junctional folds. In the left image, a terminal Schwann cell process intrudes into the primary synaptic cleft (arrow), while in the right image, the arrow points a degenerative structure in the post‐synaptic zone. (d) NMJ from U7‐ESE25–treated tibialis at 6 months post injection. Marked endplate denervation with small presynaptic boutons facing only a small portion of the numerous postsynaptic folds. In the lower image, a neuronal bouton is invaded by terminal Schwann cell processes (asterisk). Arrows point to a group of disorganized junctional folds with an abnormal enlarged secondary cleft full of degenerative vesicles. Presynaptic terminals are pseudo‐coloured in yellow, and terminal Schwann cell are pseudo‐coloured in purple. For (a–d) scale bars = 500 nm. (e) Violin plots showing the number of post‐synaptic folds normalized to synaptic length in tibialis anterior (TA) muscles of control (left, blue) and U7‐SORBS1‐ESE25–injected (right, brown) mice, 2 months post‐injection. Each data point corresponds to a serial section of NMJs, with a total of 16 NMJs analysed. **p < 0.01, unpaired Student's t‐test. (f) Table providing a summary of the NMJ alterations observed in the muscles of 6‐month‐old mice used for electron microscopy.
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