title: Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination.
abstract: 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.
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, D-37075 Goettingen, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Lappe-Siefke
authors.forename: Sandra
authors.initials: S
authors.lastname: Goebbels
authors.forename: Michel
authors.initials: M
authors.lastname: Gravel
authors.forename: Eva
authors.initials: E
authors.lastname: Nicksch
authors.forename: John
authors.initials: J
authors.lastname: Lee
authors.forename: Peter E
authors.initials: PE
authors.lastname: Braun
authors.forename: Ian R
authors.initials: IR
authors.lastname: Griffiths
authors.forename: Klaus-Armin
authors.initials: KA
authors.lastname: Nave
mesh_terms: 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
chemical_list: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases