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Max-Planck-Institut für Experimentelle Medizin
Prof. Klaus-Armin Nave

Corinna Lappe-Siefke, Dr. rer. nat.

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CNP: genetic analysis of a myelin protein associated with cytoplasmic channels and paranodal loops
in collaboration with P. Braun, Montreal, and I. Griffiths, Glasgow

The enzyme CNP (short for 2´,3´-cyclic nucleotide 3´-phosphodiesterase) is a membrane-associated protein, abundantly expressed in myelin-forming oligodendrocytes and Schwann cells. CNP is enriched in membranes that line cytoplasmic channels and paranodal loops of myelin. These microdomains link the innermost axonal zone of the myelin sheath with the glial cell soma.

Fig. 1: Colocalisation of Cre and the neuronal marker protein NeuN

The cellular function of CNP is not clear, but a role in glial process outgrowth and myelinogenesis has been suggested, based on overexpression studies in vitro. CNP may also be involved in axon-to-glia cell signalling, but the function of CNP as a structural component and/or an enzyme and its normal substrate remain obscure. To investigate the role of this myeln component in vivo, we have generated a line of transgenic mice that lack expression of the CNP gene. The development of these mutant mice and the ultrastructure of CNP-deficient myelin is under investigation.

Fig. 2: Myelination in homozygous CNP-Cre (KO) mice

n the same experiment we have followed a "knock-in" strategy and have utilized the cell type-specific activity of the CNP gene to drive expression of the recombinase Cre gene exclusively into myelin forming oligodendrocytes and Schwann cells. Cre mediated homologous recombination of genomic loxP sites can be used to study widely expressed "floxed" genes specifically in glial cells.

You may want to read more detailed information in:

Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination.
Lappe-Siefke C, Goebbels S, Gravel M, Nicksch E, Lee J, Braun PE, Griffiths IR, Nave KA.

Nat Genet. 2003 Feb, 18

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