Early ultrastructural defects of axons and axon-glia junctions in mice lacking expression of Cnp1.
Most axons in the central nervous system (CNS) are surrounded by a multilayered myelin sheath that promotes fast, saltatory conduction of electrical impulses. By insulating the axon, myelin also shields the axoplasm from the extracellular milieu. In the CNS, oligodendrocytes provide support for the long-term maintenance of myelinated axons, independent of the myelin sheath. Here, we use electron microscopy and morphometric analyses to examine the evolution of axonal and oligodendroglial changes in mice deficient in 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) and in mice deficient in both CNP and proteolipid protein (PLP/DM20). We show that CNP is necessary for the formation of a normal inner tongue process of oligodendrocytes that myelinate small diameter axons. We also show that axonal degeneration in Cnp1 null mice is present very early in postnatal life. Importantly, compact myelin formed by transplanted Cnp1 null oligodendrocytes induces the same degenerative changes in shiverer axons that normally are dysmyelinated but structurally intact. Mice deficient in both CNP and PLP develop a more severe axonal phenotype than either single mutant, indicating that the two oligodendroglial proteins serve distinct functions in supporting the myelinated axon. These observations support a model in which the trophic functions of oligodendrocytes serve to offset the physical shielding of axons by myelin membranes.
Edgar
Julia M
JM
Applied Neurobiology Group, Institute of Comparative Medicine, University of Glasgow, Bearsden, Glasgow, Scotland, United Kingdom.
McLaughlin
Mark
M
Werner
Hauke B
HB
McCulloch
Mailis C
MC
Barrie
Jennifer A
JA
Brown
Angus
A
Faichney
Andrew Blyth
AB
Snaidero
Nicolas
N
Nave
Klaus-Armin
KA
Griffiths
Ian R
IR
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000235:genetics* / Q000378:metabolism; D000200:Action Potentials / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure*; D002470:Cell Survival; D004594:Electrophysiology; D007365:Intercellular Junctions / Q000378:metabolism / Q000648:ultrastructure*; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000648:ultrastructure; D009836:Oligodendroglia / Q000378:metabolism / Q000648:ultrastructure*; D009900:Optic Nerve / Q000378:metabolism / Q000648:ultrastructure; D013116:Spinal Cord / Q000378:metabolism / Q000648:ultrastructure
D018991:Myelin Proteolipid Protein; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases