Visualization of degenerating axons in a dysmyelinating mouse mutant with axonal loss

Mice homozygously deficient for the myelin component P0 show loss of axons in peripheral nerves. In order to investigate the morphological characteristics of degenerating axons, we crossbred the myelin mutants with a transgenic mouse line expressing yellow fluorescent protein (YFP) in a small proportion of neurons. Peripheral nerves of the double mutants were prepared into small fiber bundles and investigated by fluorescence microscopy. We could identify the tips of degenerating axon as bulb-like structures. Additionally, by electron microscopy, these structures were characterized as axoplasmic extensions containing numerous membraneous compartments. By immunoelectron microscopy, the degenerating end bulbs were in contact with ensheathing Schwann cells that contained YFP-immunoreactivity possibly reflecting phagocytosis of axon material by these cells. Immunohistochemistry using antibodies against macrophages revealed that YFP-positive bulbs, but also other axonal swellings, were often associated with macrophages supporting our previous findings that myelin-related axonal loss is partially mediated by these cells.