Axonal Swellings and Degeneration in Mice Lacking the Major Proteolipid of Myelin

TLDR

Glial cells produce myelin and shape axonal morphology, and the myelin proteolipids PLP and DM20 are essential for maintaining the integrity of myelinated axons. Mice lacking PLP‑DM20 form compact myelin yet develop widespread axonal swellings and degeneration—especially in small fibers—while such swellings are absent in shiverer mice lacking MBP but reappear in MBP*PLP double mutants, indicating that impaired axonal transport and local oligodendroglial support are required for axonal survival.

Abstract

Glial cells produce myelin and contribute to axonal morphology in the nervous system. Two myelin membrane proteolipids, PLP and DM20, were shown to be essential for the integrity of myelinated axons. In the absence of PLP-DM20, mice assembled compact myelin sheaths but subsequently developed widespread axonal swellings and degeneration, associated predominantly with small-caliber nerve fibers. Similar swellings were absent in dysmyelinated shiverer mice, which lack myelin basic protein (MBP), but recurred in MBP*PLP double mutants. Thus, fiber degeneration, which was probably secondary to impaired axonal transport, could indicate that myelinated axons require local oligodendroglial support.