Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination.
Myelination of axons by oligodendrocytes enables rapid impulse propagation in the central nervous system. But long-term interactions between axons and their myelin sheaths are poorly understood. Here we show that Cnp1, which encodes 2',3'-cyclic nucleotide phosphodiesterase in oligodendrocytes, is essential for axonal survival but not for myelin assembly. In the absence of glial cyclic nucleotide phosphodiesterase, mice developed axonal swellings and neurodegeneration throughout the brain, leading to hydrocephalus and premature death. But, in contrast to previously studied myelin mutants, the ultrastructure, periodicity and physical stability of myelin were not altered in these mice. Genetically, the chief function of glia in supporting axonal integrity can thus be completely uncoupled from its function in maintaining compact myelin. Oligodendrocyte dysfunction, such as that in multiple sclerosis lesions, may suffice to cause secondary axonal loss.
Lappe-Siefke
Corinna
C
Department of Neurogenetics, Max Planck Institute of Experimental Medicine, D-37075 Goettingen, Germany.
Goebbels
Sandra
S
Gravel
Michel
M
Nicksch
Eva
E
Lee
John
J
Braun
Peter E
PE
Griffiths
Ian R
IR
Nave
Klaus-Armin
KA
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology; D005260:Female; D018390:Gene Targeting; D020271:Heredodegenerative Disorders, Nervous System / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000502:physiology*; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology; D009836:Oligodendroglia / Q000502:physiology*; D010641:Phenotype
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases