It is possible to dissociate the role of oligodendrocytes in myelination from their involvement in axonal support, according to new research published in Nature Genetics. Traditionally, both functions have been thought to be concurrent, but the study of Lappe-Siefke et al. shows that knocking out the Cnp1 gene in mice leads to axonal loss without any apparent effect on myelin structure.

Cnp1 encodes a cyclic-nucleotide phosphodiesterase (CNP) that seems to participate in RNA metabolism. Although CNP is present in oligodendrocytes and Schwann cells, its function in the nervous system is unknown. The authors knocked out the Cnp1 gene and failed to see any significant alteration in the biochemical and structural properties of myelin. However, the mutant mice developed progressive motor deficits and died prematurely. More importantly, the brains of the Cnp1−/− mice showed marked signs of degeneration that seemed to affect neurons more profoundly than oligodendrocytes. In particular, Lappe-Siefke et al. observed profuse axonal swelling that did not result from alterations of the integrity of myelin.

How CNP participates in the regulation of axonal survival remains an enigma and should be the focus of subsequent studies. But more importantly, these observations indicate that the two main functions of oligodendrocytes can be separated, and establish a double dissociation between them. So, mutations in the gene that encodes the myelin basic protein give rise to the shiverer phenotype and are associated with severe demyelination but normal axonal structure.