COPII component Sec13 is required for peripheral myelination and Schwann cell maintenance

Peripheral nerve myelination critically relies on the timely and efficient delivery of myelin proteins and membranes. Although Coat Protein Complex II (COPII) is a canonical vesicular trafficking machinery, the cell-type-specific functions of its components in Schwann cell remain uncharacterized. Here, we show that Sec13, an essential component of COPII, is abundantly expressed in Schwann cells of the sciatic nerve. Furthermore, conditional knockout of Sec13 in Schwann cells (Sec13cKO) results in hindlimb weakness and lethality in mutant mice. Morphological analysis revealed that Sec13cKO nerves are thin and translucent, with immunostaining for myelin basic protein showing a progressive reduction in myelin coverage. Transmission electron microscopy demonstrated fewer myelinated axons, loosely wrapped or absent lamellae, and an increased g-ratio, indicating thinner, poorly compacted sheaths. At the cellular level, Sec13 deletion caused a marked decrease in Sox10⁺ Schwann cell density from P7 onward, concomitant with reduced proliferation of Sox10⁺, Sox2⁺, and Oct6⁺ populations, and a significant increase of cell death at P14. Together, these findings suggest that Sec13 is indispensable for Schwann cell proliferation, survival, and execution of the myelination program.