Nature Genetics
- 33, 366 - 374 (2003)
Published online: 18 February 2003; | doi:10.1038/ng1095
Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelinationCorinna Lappe-Siefke1, Sandra Goebbels1, Michel Gravel2, Eva Nicksch1, John Lee2, Peter E. Braun2, Ian R. Griffiths3 & Klaus-Armin Nave11
Department of Neurogenetics, Max Planck Institute of Experimental Medicine, D-37075 Goettingen, Germany. 2
Department of Biochemistry, McGill University, Montreal H3G 1Y6, Canada. 3
Applied Neurobiology Group,Institute of Comparative Medicine, University of Glasgow, Bearsden, Glasgow G61 1QH, Scotland.
Correspondence should be addressed to Klaus-Armin Nave nave@em.mpg.de 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.
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promotes proliferation of oligodendrocyte progenitors and remyelination
